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Structural and functional studies on Ycf12 (Psb30) and PsbZ deletion mutants from a thermophilic cyanobacterium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ycf12 (Psb30) and PsbZ are two low-molecular weight subunits of photosystem II (PSII), with one and two trans-membrane helices, respectively. In order to study the functions of these two subunits from a structural point of view, we constructed deletion mutants lacking either Ycf12 or PsbZ from Thermosynechococcus elongatus, and purified, crystallized and analyzed the structure of PSII dimer from the two mutants. Our results showed that Ycf12 is located in the periphery of PSII, close to PsbK, PsbZ and PsbJ, and corresponded to the unassigned helix X1 reported previously, in agreement with the recent structure at 2.9 A ...
Source: Mol Biol Cell - November 13, 2009 Category: Molecular Biology Authors: Takasaka K, Iwai M, Umena Y, Kawakami K, Ohmori Y, Ikeuchi M, Takahashi Y, Kamiya N, Shen JR Tags: Biochim Biophys Acta Source Type: journals

A Novel JNK Binding Protein WDR62 Is Recruited to Stress Granules and Mediates a Non-classical JNK Activation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Jonathan Chernoff The c-Jun N-terminal kinase (JNK) is part of a Mitogen-activated protein kinase (MAPK) signaling cascade. Scaffold proteins simultaneously associate with various components of the MAPK signaling pathway and play a role in signal transmission and regulation. Here we describe the identification of a novel scaffold JNK binding protein, WDR62, with no sequence homology to any of the known scaffold proteins. WDR62 is a ubiquitously expressed heat-sensitive 175 kDa protein that specifically associates with JNK but not with ERK and p38. Association between WDR62 and JNKs occurs in the abse...
Source: Mol Biol Cell - November 12, 2009 Category: Molecular Biology Authors: Wasserman T, Katsenelson K, Daniliuc S, Hasin T, Choder M, Aronheim A Tags: Mol Biol Cell Source Type: journals

Mobility, Microtubule Nucleation and Structure of MTOCs in Multinucleated Hyphae of Ashbya gossypii.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Kerry S. Bloom We investigated the migration of multiple nuclei in hyphae of the filamentous fungus Ashbya gossypii. Three types of cytoplasmic microtubule (cMT)-dependent nuclear movements were characterized using live cell imaging: short range oscillations (up to 4.5 mum/min), rotations (up to 180 degrees in 30 s) and long-range nuclear bypassing (up to 9 mum/min). These movements were superimposed on a cMT-independent mode of nuclear migration, cotransport with the cytoplasmic stream. This latter mode is sufficient to support wild-type-like hyphal growth speeds. cMT-dependent nuclear movements wer...
Source: Mol Biol Cell - November 12, 2009 Category: Molecular Biology Authors: Lang C, Grava S, van den Hoorn T, Trimble R, Philippsen P, Jaspersen SL Tags: Mol Biol Cell Source Type: journals

Centromeric Localization of Dispersed Pol III Genes in Fission Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present evidence that Pol III transcribed genes such as tRNA and 5S rRNA genes can localize to centromeres and contribute to a global genome organization. Furthermore, we find that ectopic insertion of Pol III genes into a nonPol III gene locus results in the centromeric localization of the locus. We show that the centromeric localization of Pol III genes is mediated by condensin, which interacts with the Pol III transcription machinery, and that transcription levels of the Pol III genes are negatively correlated with the centromeric localization of Pol III genes. This centromeric localization of Pol III genes initially...
Source: Mol Biol Cell - November 12, 2009 Category: Molecular Biology Authors: Iwasaki O, Tanaka A, Tanizawa H, Grewal SI, Noma KI Tags: Mol Biol Cell Source Type: journals

Mechanisms of Self-organization of Cortical Microtubules in Plants Revealed by Computational Simulations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: David G. Drubin Microtubules confined to the two-dimensional cortex of elongating plant cells must form a parallel yet dispersed array transverse to the elongation axis for proper cell wall expansion. Some of these microtubules exhibit free minus-ends, leading to migration at the cortex by hybrid treadmilling. Collisions between microtubules can result in plus-end entrainment ("zippering") or rapid depolymerization. Here, we present a computational model of cortical microtubule organization. We find that plus-end entrainment leads to self-organization of microtubules into parallel arrays, while catas...
Source: Mol Biol Cell - November 12, 2009 Category: Molecular Biology Authors: Allard JF, Wasteneys GO, Cytrynbaum EN Tags: Mol Biol Cell Source Type: journals

Actin Binding Protein-1 Interacts with WIP to Regulate Growth Factor-induced Dorsal Ruffle Formation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Josephine C. Adams Growth factor stimulation induces the formation of dynamic actin structures known as dorsal ruffles. Mammalian actin binding protein-1 (mAbp1) is an actin binding protein that has been implicated in regulating clathrin-mediated endocytosis; however, a role for mAbp1 in regulating the dynamics of growth factor-induced actin-based structures has not been defined. Here we show that mAbp1 localizes to dorsal ruffles and is necessary for platelet-derived growth factor (PDGF)-mediated dorsal ruffle formation. Despite their structural similarity, we find that mAbp1 and cortactin have nonr...
Source: Mol Biol Cell - November 12, 2009 Category: Molecular Biology Authors: Cortesio CL, Perrin BJ, Bennin DA, Huttenlocher A Tags: Mol Biol Cell Source Type: journals

Age-dependent Preferential Dense-core Vesicle Exocytosis in Neuroendocrine Cells Revealed by Newly Developed Monomeric Fluorescent Timer Protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Akihiko Nakano Although it is evident that only a few secretory vesicles accumulating in neuroendocrine cells are qualified to fuse with the plasma membrane and release their contents to the extracellular space, the molecular mechanisms that regulate their exocytosis are poorly understood. For example, it has been controversial whether secretory vesicles are exocytosed randomly or preferentially according to their age. Using a newly developed protein-based fluorescent timer, mK-GO, which changes color with a predictable time course, here we show that small GTPase Rab27A effectors regulate age-depende...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Tsuboi T, Kitaguchi T, Karasawa S, Fukuda M, Miyawaki A Tags: Mol Biol Cell Source Type: journals

Growth-limiting Intracellular Metabolites in Yeast Growing Under Diverse Nutrient Limitations.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Charles Boone Microbes tailor their growth rate to nutrient availability. Here we measured, using liquid chromatography-mass spectrometry, more than 100 intracellular metabolites in steady-state cultures of S. cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity. Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low int...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD Tags: Mol Biol Cell Source Type: journals

Molecular Architecture of Synaptic Actin Cytoskeleton in Hippocampal Neurons Reveals a Mechanism of Dendritic Spine Morphogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Paul Forscher Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament netw...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Korobova F, Svitkina T Tags: Mol Biol Cell Source Type: journals

Novel Role of ATPase Subunit C Targeting Peptides Beyond Mitochondrial Protein Import.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Thomas D. Fox In mammals, subunit c of the F1F0-ATP synthase has three isoforms (P1, P2, P3). These isoforms differ by their cleavable mitochondrial targeting peptides, while the mature peptides are identical. To investigate this apparent genetic redundancy we knocked down each of the three subunit c isoform by RNA interference in HeLa cells. Silencing any of the subunit c isoforms individually resulted in an ATP synthesis defect, indicating that these isoforms are not functionally redundant. We found that subunit c knock down impaired the structure and function of the mitochondrial respiratory chain...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Vives-Bauza C, Magrané J, Andreu AL, Manfredi G Tags: Mol Biol Cell Source Type: journals

Sec3-containing Exocyst Complex Is Required for Desmosome Assembly in Mammalian Epithelial Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Patrick J. Brennwald The Exocyst is a conserved multi-subunit complex involved in the docking of post-Golgi transport vesicles to sites of membrane remodeling during cellular processes such as polarization, migration and division. In mammalian epithelial cells, Exocyst complexes are recruited to nascent sites of cell-cell contact in response to E-cadherin-mediated adhesive interactions, and this event is an important early step in the assembly of intercellular junctions. Sec3 has been hypothesized to function as a spatial landmark for the development of polarity in budding yeast, but its role in epit...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Andersen NJ, Yeaman C Tags: Mol Biol Cell Source Type: journals

Hsp90 Nuclear Accumulation in Quiescence Is Linked to Chaperone Function and Spore Development in Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Benjamin S. Glick Hsp90 operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent S. cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sba1. Translocation of both chaperones was dependent on the alpha/beta importin SRP1/KAP95. Hsp90 nuclear retention was coincident with glucose exhaustion and appears to be a starvation-specific response, as heat shock or 10% ethanol str...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Tapia H, Morano KA Tags: Mol Biol Cell Source Type: journals

Rad4 Regulates Protein Turnover at a Postubiquitylation Step.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Jeffrey L. Brodsky The Ub-binding protein Rad23 plays an important role in facilitating the transfer of substrates to the proteasome. However, the mechanism underlying Rad23's function in proteolysis remains unknown. Here, we demonstrate that Rad4, a Rad23-binding protein, also regulates ubiquitylated substrate turnover. Rad4 was previously known only as a key repair factor which directly recognizes DNA damage and initiates DNA repair. Our results, however, reveal a novel function of Rad4. We found that Rad4 and Rad23 share several common substrates. Substrates in rad4Delta cells are ubiquitylated, i...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Li Y, Yan J, Kim I, Liu C, Huo K, Rao H Tags: Mol Biol Cell Source Type: journals

Hydrogen Sulfide Increases HIF-1 Activity Independent of VHL-1 in C. elegans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: William P. Tansey Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor HIF-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here we show that C. elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis while hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. ...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Budde MW, Roth MB Tags: Mol Biol Cell Source Type: journals

NHERF1 Overexpression-dependent Increase of Cytoskeleton Organization Is Fundamental in the Rescue of F508del CFTR in Human Airway CFBE41o- Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Keith E. Mostov We have demonstrated that NHERF1 overexpression in CFBE41o- cells induces a significant redistribution of F508del CFTR from the cytoplasm to the apical membrane and rescues CFTR-dependent chloride secretion. Here, we observe that CFBE41o- monolayers displayed substantial disassembly of actin filaments and that overexpression of wt NHERF1 but not NHERF1-DeltaERM increased F-actin assembly and organization. Further, the dominant negative FERM domain of ezrin reversed the wt NHERF1 overexpression-induced increase in both F-actin and CFTR-dependent chloride secretion. wt NHERF1 overexpres...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Favia M, Guerra L, Fanelli T, Cardone RA, Monterisi S, Di Sole F, Castellani S, Chen M, Seidler U, Reshkin SJ, Conese M, Casavola V Tags: Mol Biol Cell Source Type: journals

Analyzing the Effects of Delaying Aster Separation on Furrow Formation during Cytokinesis in the C. elegans Embryo.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Yu-Li Wang Signaling by the centrosomal asters and spindle midzone coordinately directs formation of the cytokinetic furrow. Here, we explore the contribution of the asters by analyzing the consequences of altering interaster distance during the first cytokinesis of the C. elegans embryo. Delaying aster separation, using TPXL-1 depletion to shorten the metaphase spindle, leads to a corresponding delay in furrow formation, but results in a single furrow that ingresses at a normal rate. Preventing aster separation, by simultaneously inhibiting TPXL-1 and Galpha signaling-based cortical forces pulling o...
Source: Mol Biol Cell - November 4, 2009 Category: Molecular Biology Authors: Lewellyn L, Dumont J, Desai A, Oegema K Tags: Mol Biol Cell Source Type: journals

Receptor Type Protein Tyrosine Phosphatase-Kappa (RPTP-{kappa}) Mediates Cross-Talk between TGF-{beta} and EGFR Signaling Pathways in Human Keratinocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that RPTP-kappa mediates functional integration of EGFR and TGF-beta signaling pathways in human keratinocytes. TGF-beta up-regulates RPTP-kappa mRNA and protein, in a dose and time dependent manner. Induction of RPTP-kappa by TGF-beta significantly decreases basal and EGF-stimulated EGFR tyrosine phosphorylation. shRNA-mediated reduction of TGF-beta-induced RPTP-kappa significantly attenuates the ability of TGF-beta to inhibit proliferation. RPTP-kappa induction is dependent on activation of transcription factors Smad3 and Smad4. Inhibition of TGF-beta receptor kinase completely prevents induction of RPTP-k...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Xu Y, Baker D, Quan T, Baldassare JJ, Voorhees JJ, Fisher GJ Tags: Mol Biol Cell Source Type: journals

Role of Rap1B and Tumor Suppressor PTEN in the Negative Regulation of Lysophosphatidic Acid-induced Migration by Isoproterenol in Glioma Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we have focused on the negative regulation of lysophosphatidic acid (LPA)-induced migration in glioma cells. Using small-interference RNA and dominant-negative gene strategies in addition to pharmacological tools, we found that isoproterenol (ISO) and sphingosine-1-phosphate (S1P) negatively but differently regulate the LPA-induced migration. ISO-induced suppression of the migration of glioma cells occurs via beta2-adrenergic receptor/cAMP/Epac/Rap1B/inhibition of Rac, whereas S1P has been shown to suppress the migration of the cells through S1P2 receptor/Rho-mediated down-regulation of Rac1. The expression ...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Malchinkhuu E, Sato K, Maehama T, Ishiuchi S, Yoshimoto Y, Mogi C, Kimura T, Kurose H, Tomura H, Okajima F Tags: Mol Biol Cell Source Type: journals

The E3 Ubiquitin Ligases Hrd1 and gp78 Bind to and Promote Cholera Toxin Retro-translocation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Ramanujan S. Hegde To cause disease, cholera toxin (CT) is transported from the cell surface to the endoplasmic reticulum (ER) lumen where the catalytic CTA1 subunit retro-translocates to the cytosol to induce pathological water secretion. Two retro-translocon components are the Derlins and ER-associated multi-spanning E3 ubiquitin ligases including Hrd1 and gp78. We demonstrated previously that Derlin-1 facilitates CTA1 retro-translocation. However, as CTA1 is neither ubiquitinated on lysines nor at its N-terminus, the role of E3 ligases in toxin retro-translocation is unclear. Here, we show that ex...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Bernardi KM, Williams JM, Kikkert M, van Voorden S, Wiertz EJ, Ye Y, Tsai B Tags: Mol Biol Cell Source Type: journals

MICAL-L1 Links EHD1 to Tubular Recycling Endosomes and Regulates Receptor Recycling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Sandra L. Schmid Endocytic recycling of receptors and lipids occurs via a complex network of tubular and vesicular membranes. EHD1 is a key regulator of endocytosis and associates with tubular membranes to facilitate recycling. Although EHD proteins tubulate membranes in vitro, EHD1 primarily associates with pre-existing tubules in vivo. How EHD1 is recruited to these tubular endosomes remains unclear. We have determined that the Rab8-interacting protein, MICAL-L1, associates with EHD1, with both proteins colocalizing to long tubular membranes, in vitro and in live cells. MICAL-L1 is a largely unchar...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Sharma M, Panapakkam Giridharan SS, Rahajeng J, Naslavsky N, Caplan S Tags: Mol Biol Cell Source Type: journals

Roles of Formin Nodes and Myosin Motor Activity in Mid1p-dependent Contractile-Ring Assembly during Fission Yeast Cytokinesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Daniel J. Lew Two prevailing models have emerged to explain the mechanism of contractile-ring assembly during cytokinesis in the fission yeast Schizosaccharomyces pombe: the spot/leading cable model and the search, capture, pull, and release (SCPR) model. We tested some of the basic assumptions of the two models. Monte Carlo simulations of the SCPR model require that the formin Cdc12p is present in >30 nodes from which actin filaments are nucleated and captured by myosin-II in neighboring nodes. The force produced by myosin motors pulls the nodes together to form a compact contractile ring. Live m...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Coffman VC, Nile AH, Lee IJ, Liu H, Wu JQ Tags: Mol Biol Cell Source Type: journals

Mammalian pre-mRNA 3' End Processing Factor CF Im68 Functions in mRNA Export.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Marvin Wickens Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3' end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3' end processing complex, CF Im68, stimulates mRNA export. CF Im68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF Im68 may act as a novel a...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Ruepp MD, Aringhieri C, Vivarelli S, Cardinale S, Paro S, Schümperli D, Barabino SM Tags: Mol Biol Cell Source Type: journals

Drosophila Lysophospholipid Acyltransferases Are Specifically Required for Germ Cell Development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Marcos Gonzalez-Gaitan Enzymes of the membrane-bound O-acyltransferase (MBOAT) family add fatty acyl chains to a diverse range of protein and lipid substrates. A chromosomal translocation disrupting human MBOAT1 results in a novel syndrome characterized by male sterility and brachydactyly. We have found that the Drosophila homologues of MBOAT1, Oysgedart (Oys), Nessy (Nes) and Farjavit (Frj), are lysophospholipid acyltransferases. When expressed in yeast, these MBOATs esterify specific lysophospholipids preferentially with unsaturated fatty acids. Generating null mutations for each gene allowed us to...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Steinhauer J, Gijón MA, Riekhof WR, Voelker DR, Murphy RC, Treisman JE Tags: Mol Biol Cell Source Type: journals

The Nup107-160 Nucleoporin Complex Promotes Mitotic Events via Control of the Localisation State of the Chromosome Passenger Complex.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Karsten Weis The human Nup107-160 nucleoporin complex plays a major role in formation of the nuclear pore complex and is localized to kinetochores in mitosis. Here we report that Seh1, a component of the Nup107-160 complex, functions in chromosome alignment and segregation by regulating the centromeric localization of Aurora B and other chromosome passenger complex proteins. Localization of CENP-E is not affected by Seh1 depletion and analysis by electron microscopy showed that microtubule kinetochore attachments are intact. Seh1-depleted cells show impaired Aurora B localization, which results in se...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Platani M, Santarella-Mellwig R, Posch M, Walczak R, Swedlow JR, Mattaj IW Tags: Mol Biol Cell Source Type: journals

Retrograde Neurotrophic Signaling Requires a Protein Interacting with Receptor Tyrosine Kinases via C2H2 Zinc Fingers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Mark H. Ginsberg Neurotrophins at axonal terminals signal to cell bodies to regulate neuronal development via signaling endosomes containing activated Trk receptor tyrosine kinases and mitogen-activated protein kinases (MAPKs). Requirements for the formation of signaling endosomes remain, however, poorly characterized. Here we show that a novel Trk-interacting protein, NTRAP (neurotrophic factor receptor associated protein), plays a crucial role in this signaling process. NTRAP interacts with the Trk intracellular domain through its C2H2 zinc fingers in a kinase-dependent manner. It is associated wit...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Fu X, Zang K, Zhou Z, Reichardt LF, Xu B Tags: Mol Biol Cell Source Type: journals

PI(3,4,5)P3 Localization in Recycling Endosomes Is Necessary for AP-1B-dependent Sorting in Polarized Epithelial Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, PI(3,4,5)P3 formation in recycling endosomes is essential for AP-1B function. PMID: 19864464 [PubMed - as supplied by publisher] (Source: Mol Biol Cell)
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Fields IC, King SM, Shteyn E, Kang RS, Fölsch H Tags: Mol Biol Cell Source Type: journals

A Novel Mouse HSF3 Has the Potential to Activate Non-classical Heat Shock Genes during Heat Shock.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: M. Bishr Omary The heat shock response is characterized by the expression of a set of classical heat shock genes, and is regulated by heat shock transcription factor 1 (HSF1) in mammals. However, comprehensive analyses of gene expression have revealed very large numbers of inducible genes in cells exposed to heat shock. It is believed that HSF1 is required for the heat-inducible expression of these genes although HSF2 and HSF4 modulate some of the gene expression. Here, we identified a novel mouse HSF3 (mHSF3) translocated into the nucleus during heat shock. However, mHSF3 did not activate classical ...
Source: Mol Biol Cell - October 28, 2009 Category: Molecular Biology Authors: Fujimoto M, Hayashida N, Katoh T, Oshima K, Shinkawa T, Prakasam R, Tan K, Inouye S, Takii R, Nakai A Tags: Mol Biol Cell Source Type: journals

Small Cajal Body-Specific RNAs (scaRNAs) of Drosophila Function in the Absence of Cajal Bodies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: A. Gregory Matera During their biogenesis small nuclear RNAs (snRNAs) undergo multiple covalent modifications that require guide RNAs to direct methylase and pseudouridylase enzymes to the appropriate nucleotides. Because of their localization in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific RNAs (scaRNAs). Using a fluorescent primer extension technique, we mapped the modified nucleotides in Drosophila U1, U2, U4 and U5 snRNAs. By fluorescent in situ hybridization (FISH) we showed that seven Drosophila scaRNAs are concentrated in easily detectable CBs. We used two assay...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Deryusheva S, Gall JG Tags: Mol Biol Cell Source Type: journals

Bub3p Facilitates Spindle Checkpoint Silencing in Fission Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Daniel J. Lew Although critical for spindle checkpoint signaling, the role kinetochores play in APC inhibition remains unclear. Here we show that spindle checkpoint proteins are severely depleted from unattached kinetochoresin fission yeast cells lacking Bub3p. Surprisingly, a robust mitotic arrest is maintained in the vast majority of bub3Delta cells, yet they die, suggesting that Bub3p is essential for successful checkpoint recovery. During recovery, two defects are observed: 1) cells mis-segregate chromosomes and 2) anaphase onset is significantly delayed. We show that Bub3p is required to activat...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Vanoosthuyse V, Meadows JC, van der Sar SJ, Millar JB, Hardwick KG Tags: Mol Biol Cell Source Type: journals

Synthetic Lethal Genetic Interactions that Decrease Somatic Cell Proliferation in C. elegans Identify the Alternative RFCCTF18 as a Candidate Cancer Drug Target.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: David G. Drubin Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six S. cerevisiae CIN genes orthologous to genes mutated in colon tumors and five unlinked CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing sy...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: McLellan J, O'Neil N, Tarailo S, Stoepel J, Bryan J, Rose A, Hieter P Tags: Mol Biol Cell Source Type: journals

Binding the Atypical RA Domain of Ste50p to the Unfolded Opy2p Cytoplasmic Tail Is Essential for HOG Pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Charles Boone Activation of the high osmolarity glycerol (HOG) pathway for osmoregulation in the yeast S. cerevisiae involves interaction of the adaptor Ste50p with the cytoplasmic tail of single-transmembrane protein Opy2p. We have determined the solution structure of the Ste50p-RA domain, and it shows an atypical RA fold lacking the beta1 and beta2 strands of the canonical motif. While the core of the RA domain is fully functional in the pheromone response, an additional region is required for the HOG pathway activation. Two peptide motifs within the intrinsically disordered cytoplasmic tail of Opy...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Ekiel I, Sulea T, Jansen G, Kowalik M, Minailiuc O, Cheng J, Harcus D, Cygler M, Whiteway M, Wu C Tags: Mol Biol Cell Source Type: journals

Bone Morphogenetic Protein-6 Promotes Cerebellar Granule Neuron Survival by Activation of the MEK/ERK/CREB Pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Marianne Bronner-Fraser Bone morphogenetic proteins (BMPs) have been implicated in the generation and postnatal differentiation of cerebellar granule cells (CGCs). Here, we examined the eventual role of BMPs on the survival of these neurons. Lack of depolarization causes CGCs death by apoptosis in vivo, a phenomenon that is mimicked in vitro by deprivation of high potassium in cultured CGCs. We have found that BMP-6, but not BMP-7, is able to block low potassium-mediated apoptosis in CGCs. The neuroprotective effect of BMP-6 is not accompanied by an increase of Smad translocation to the nucleus, sugg...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Barneda-Zahonero B, Miñano-Molina A, Badiola N, Fadó R, Xifró X, Saura CA, Rodríguez-Alvarez J Tags: Mol Biol Cell Source Type: journals

MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Richard K. Assoian The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not yet been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MB...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Hsu KW, Hsieh RH, Wu CW, Chi CW, Lee YH, Kuo ML, Wu KJ, Yeh TS Tags: Mol Biol Cell Source Type: journals

Exploring the Roles of Diaphanous and Enabled Activity in Shaping the Balance between Filopodia and Lamellipodia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Marcos Gonzalez-Gaitan During migration cell protrusions power cell extension and sample the environment. Different cells produce different protrusions, from keratocytes dominated by lamellipodia, to growth cones combining filopodia and lamellipodia, to dendritic spines. One key challenge is to determine how the toolkit of actin regulators are coordinated to generate these diverse protrusive arrays. Here we use Drosophila leading-edge cells to explore how Diaphanous-related formins and Ena/VASP proteins cooperate in this process. We first dissect the Diaphanous-regulatory region, revealing novel role...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Homem CC, Peifer M Tags: Mol Biol Cell Source Type: journals

Neuronal IP3 3-Kinase Is an F-actin Bundling Protein: Role in Dendritic Targeting and Regulation of Spine Morphology.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Paul Forscher The actin microstructure in dendritic spines is involved in synaptic plasticity. Inositol trisphosphate 3-kinase A (ITPKA) terminates Ins(1,4,5)P3 signals emanating from spines and also binds filamentous actin (F-actin) through its amino terminal region (amino acids 1-66, N66). Here we investigated how ITPKA, independent of its kinase activity, regulates dendritic spine F-actin microstructure. We show that the N66 region of the protein mediates F-actin bundling. An N66 fusion protein bundled F-actin in vitro, and the bundling involved N66 dimerization. By mutagenesis we identified a poi...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Johnson HW, Schell MJ Tags: Mol Biol Cell Source Type: journals

Notch Signaling and Developmental Cell-Cycle Arrest in Drosophila Polar Follicle Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Marcos Gonzalez-Gaitan Temporal and spatial regulation of cell division is critical for proper development of multicellular organisms. An important aspect of this regulation is cell-cycle arrest, which in many cell types is coupled with differentiated status. Here we report that the polar cells-a group of follicle cells differentiated early during Drosophila oogenesis-are arrested at G2 phase and can serve as a model cell type for investigation of developmental regulation of cell-cycle arrest. On examining the effects of String, a mitosis-promoting phosphatase Cdc25 homolog, and Notch signaling in po...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Shyu LF, Sun J, Chung HM, Huang YC, Deng WM Tags: Mol Biol Cell Source Type: journals

Mitochondrial ROS Mediates GPCR-induced TACE-dependent TGF-{alpha} Shedding.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that ATP stimulates TGF-alpha proteolysis with concomitant EGFR activation and that this process requires ADAM17/TACE activity in both murine fibroblasts and CHO cells. ATP-induced TGF-alpha shedding required calcium and was independent of Src family kinases, PKC and MAPK signaling. Moreover, ATP-induced TGF-alpha shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Furthermore, hydrogen peroxide restored TGF-alpha shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasm...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Myers TJ, Brennaman LH, Stevenson M, Higashiyama S, Russell WE, Lee DC, Sunnarborg SW Tags: Mol Biol Cell Source Type: journals

Distinct Roles for CARMIL Isoforms in Cell Migration.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Yu-Li Wang Molecular mechanisms for cell migration, especially how signaling and cytoskeletal systems are integrated, are not understood well. Here, we examined the role of CARMIL (Capping protein, Arp2/3, and Myosin-I Linker) family proteins in migrating cells. Vertebrates express three conserved genes for CARMIL, and we examined the functions of the two CARMIL genes expressed in migrating human cultured cells. Both isoforms, CARMIL1 and CARMIL2, were necessary for cell migration, but for different reasons. CARMIL1 localized to lamellipodia and macropinosomes, and loss of its function caused loss of...
Source: Mol Biol Cell - October 20, 2009 Category: Molecular Biology Authors: Liang Y, Niederstrasser H, Edwards M, Jackson CE, Cooper JA Tags: Mol Biol Cell Source Type: journals

Phosphatidylserine Regulation of Ca2+-Triggered Exocytosis and Fusion Pores in PC12 Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Patrick J. Brennwald The synaptic vesicle protein synaptotagmin I (Syt I) binds phosphatidylserine (PS) in a Ca(2+)-dependent manner. This interaction is thought to play a role in exocytosis, but its precise functions remain unclear. To determine potential roles for Syt I-PS binding we varied the PS content in PC12 cells and liposomes, and studied the effects on the kinetics of exocytosis and Syt I binding in parallel. Raising PS produced a steeply nonlinear, saturating increase in Ca(2+)-triggered fusion, and a graded slowing of the rate of fusion pore dilation. Ca(2+)-Syt I bound liposomes more tig...
Source: Mol Biol Cell - October 13, 2009 Category: Molecular Biology Authors: Zhang Z, Hui E, Chapman ER, Jackson MB Tags: Mol Biol Cell Source Type: journals

Requirements for Recruitment of a G Protein-coupled Receptor to Clathrin-coated Pits in Budding Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Howard Riezman Endocytic internalization of G protein-coupled receptors (GPCRs) plays a critical role in down-regulation of GPCR signaling. The yeast mating pheromone receptor, Ste2p, has been used as a model to investigate mechanisms of signal transduction, modification, and endocytic internalization of GPCRs. We previously used a fluorescently labeled mating pheromone derivative to reveal unappreciated molecular and spatio-temporal features of GPCR endocytosis in budding yeast. Here we identify recruitment of Ste2p to pre-existing clathrin-coated pits (CCPs) as a key step regulated by receptor phos...
Source: Mol Biol Cell - October 13, 2009 Category: Molecular Biology Authors: Toshima JY, Nakanishi JI, Mizuno K, Toshima J, Drubin DG Tags: Mol Biol Cell Source Type: journals

The CORVET Subunit Vps8 Cooperates with the Rab5 Homolog Vps21 to Induce Clustering of Late Endosomal Compartments.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Patrick J. Brennwald Membrane tethering, the process of mediating the first contact between membranes destined for fusion, requires specialized multisubunit protein complexes and Rab GTPases. In the yeast endolysosomal system, the hexameric HOPS tethering complex cooperates with the Rab7 homolog Ypt7 to promote homotypic fusion at the vacuole, whereas the recently identified homologous CORVET complex acts at the level of late endosomes. Here, we have further functionally characterized the CORVET-specific subunit Vps8 and its relationship to the remaining subunits using an in vivo approach that allows...
Source: Mol Biol Cell - October 13, 2009 Category: Molecular Biology Authors: Markgraf DF, Ahnert F, Arlt H, Mari M, Peplowska K, Epp N, Griffith J, Reggiori F, Ungermann C Tags: Mol Biol Cell Source Type: journals

Oxidative Stress Inhibits Nuclear Protein Export by Multiple Mechanisms which Target FG Nucleoporins and Crm1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Kunxin Luo Nuclear transport of macromolecules is regulated by the physiological state of the cell and thus sensitive to stress. To define the molecular mechanisms that control nuclear export upon stress, cells were exposed to nonlethal concentrations of the oxidant diethyl maleate (DEM). These stress conditions inhibited Crm1-dependent nuclear export and increased the association between Crm1 and Ran. In addition, we identified several repeat-containing nucleoporins implicated in nuclear export as targets of oxidative stress. As such, DEM treatment reduced Nup358 levels at the nuclear envelope and r...
Source: Mol Biol Cell - October 13, 2009 Category: Molecular Biology Authors: Crampton N, Kodiha M, Shrivastava S, Umar R, Stochaj U Tags: Mol Biol Cell Source Type: journals

Myosin IXa Regulates Epithelial Differentiation and Its Deficiency Results in Hydrocephalus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here that mice deficient for myosin IXa (Myo9a), an actin-dependent motor molecule with a Rho GTPase activating (GAP) domain, develop severe hydrocephalus with stenosis and closure of the ventral caudal 3rd ventricle and the aqueduct. Myo9a is expressed in maturing ependymal epithelial cells and its absence leads to impaired maturation of ependymal cells. The Myo9a deficiency further resulted in a distorted ependyma due to irregular epithelial cell morphology and altered organization of intercellular junctions. Ependymal cells occasionally delaminated forming multilayered structures that bridged the CSF-filled ve...
Source: Mol Biol Cell - October 13, 2009 Category: Molecular Biology Authors: Abouhamed M, Grobe K, Leefa Chong San IV, Thelen S, Honnert U, Balda MS, Matter K, Bähler M Tags: Mol Biol Cell Source Type: journals

Brd4 Marks Select Genes on Mitotic Chromatin and Directs Post-mitotic Transcription.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Yixian Zheng On entry into mitosis, many transcription factors dissociate from chromatin, resulting in global transcriptional shutdown. During mitosis, some genes are marked to ensure the inheritance of their expression in the next generation of cells. The nature of mitotic gene marking, however, has been obscure. Brd4 is a double bromodomain protein that localizes to chromosomes during mitosis, and is implicated in holding mitotic memory. In interphase, Brd4 interacts with P-TEFb and functions as a global transcriptional coactivator. We found that throughout mitosis, Brd4 remained bound to the trans...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Dey A, Nishiyama A, Karpova T, McNally J, Ozato K Tags: Mol Biol Cell Source Type: journals

The Exomer Coat Complex Transports Fus1p to the Plasma Membrane via a Novel Plasma Membrane Sorting Signal in Yeast.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Benjamin S. Glick Sorting of transmembrane cargo proteins to different cellular compartments is mediated by sorting signals that are recognized by coat proteins involved in vesicle biogenesis. We have identified a sorting signal in the yeast cell fusion protein Fus1p that is required for its transport from the trans-Golgi compartment to the plasma membrane. Transport of Fus1p from the trans-Golgi to the cell surface is dependent on Chs5p, a component of the multisubunit exomer complex. We show that Fus1p transport is also dependent on the exomer components Bch1p and Bud7p. Disruption of the clathrin ...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Barfield RM, Fromme JC, Schekman R Tags: Mol Biol Cell Source Type: journals

Tight Functional Coupling of Kinesin-1A and Dynein Motors in the Bidirectional Transport of Neurofilaments.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Erika L. Holzbaur We have tested the hypothesis that kinesin-1A (formerly KIF5A) is an anterograde motor for axonal neurofilaments. In cultured sympathetic neurons from kinesin-1A knockout mice, we observed a 75% reduction in the frequency of both anterograde and retrograde neurofilament movement. This transport defect could be rescued by kinesin-1A, and with successively decreasing efficacy by kinesin-1B and kinesin-1C. In wild type neurons, headless mutants of kinesin-1A and kinesin-1C inhibited both anterograde and retrograde movement in a dominant negative manner. Because dynein is thought to be ...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Uchida A, Alami NH, Brown A Tags: Mol Biol Cell Source Type: journals

Evidence that Electrostatic Interactions between VAMP2 and Acidic Phospholipids May Modulate the Fusion of Transport Vesicles with the Plasma Membrane.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Thomas F.J. Martin The juxtamembrane domain of VAMP2 contains a conserved cluster of basic/hydrophobic residues that may play an important role in membrane fusion. Our measurements on peptides corresponding to this domain determine the electrostatic and hydrophobic energies by which this domain of VAMP2 could bind to the adjacent lipid bilayer in an insulin granule or other transport vesicle. Mutation of residues within the juxtamembrane domain that reduce the VAMP2 net positive charge, and thus its interaction with membranes, inhibits secretion of insulin granules in beta cells. Increasing salt conc...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Williams D, Vicogne J, Zaitseva I, McLaughlin S, Pessin JE Tags: Mol Biol Cell Source Type: journals

RhoG Promotes Neural Progenitor Cell Proliferation in Mouse Cerebral Cortex.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: J. Silvio Gutkind In early cortical development, neural progenitor cells (NPCs) expand their population in the ventricular zone (VZ), and produce neurons. Although a series of studies have revealed the process of neurogenesis, the molecular mechanisms regulating NPC proliferation are still largely unknown. Here we found that RhoG, a member of Rho family GTPases, was expressed in the VZ at early stages of cortical development. Expression of constitutively active RhoG promoted NPC proliferation and incorporation of bromodeoxyuridine (BrdU) in vitro, and the proportion of Ki67-positive cells in vivo. In...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Fujimoto S, Negishi M, Katoh H Tags: Mol Biol Cell Source Type: journals

Dcp1-Bodies in Mouse Oocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: A. Gregory Matera Processing bodies (P-bodies) are cytoplasmic granules involved in the storage and degradation of mRNAs. In somatic cells, their formation involves miRNA-mediated mRNA silencing. Many P-body protein components are also found in germ cell granules, such as in mammalian spermatocytes. In fully grown mammalian oocytes, where changes in gene expression depend entirely on translational control, RNA granules have not as yet been characterized. Here we show the presence of P-body-like foci in mouse oocytes, as revealed by the presence of Dcp1a and the colocalization of RNA associated protei...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Swetloff A, Conne B, Huarte J, Pitetti JL, Nef S, Vassalli JD Tags: Mol Biol Cell Source Type: journals

Rescue of Munc18-1 and -2 Double Knockdown Reveals the Essential Functions of Interaction between Munc18 and Closed Syntaxin in PC12 Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Monitoring Editor: Keith E. Mostov Munc18-1 binds to syntaxin-1A via two distinct sites referred to as the 'closed' conformation and N-terminus binding. The latter has been shown to stimulate SNARE-mediated exocytosis, whereas the former is believed to be inhibitory or dispensable. To precisely define the contributions of each binding mode, we have engineered Munc18-1/-2 double knockdown neurosecretory cells and show that not only syntaxin-1A and -1B but also syntaxin-2 and -3 were significantly reduced as a result of Munc18-1 and -2 knockdown. Syntaxin-1 was mislocalized and the regulated secretion was abolished. We n...
Source: Mol Biol Cell - October 6, 2009 Category: Molecular Biology Authors: Han L, Jiang T, Han GA, Malintan NT, Xie L, Wang L, Tse FW, Gaisano HY, Collins BM, Meunier FA, Sugita S Tags: Mol Biol Cell Source Type: journals