Abstract:
: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 soluble N-ethylmaleimide-sensitive factor attachment protein receptor-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 are significantly reduced as a result of Munc18-1 and -2 knockdown. Syntaxin-1 was mislocalized and the regulated secretion was abolished. We next examined the abilities of Munc18-1 mutants to rescue the defective phenotypes. Mutation (K46E/E59K) of Munc18-1 that selectively prevents binding to closed syntaxin-1 was unable to restore syntaxin-1 expression, localization, or secretion. In contrast, mutations (F115E/E132A) of Munc18-1 that selectively impair binding to the syntaxin-1 N terminus could still rescue the defective phenotypes. Our results indicate that Munc18-1 and -2 act in concert to support the expression of a broad range of syntaxins and to deliver syntaxin-1 to the plasma membrane. Our studies also indicate that the binding to the closed conformation of syntaxin is essential for Munc18-1 stimulatory action, whereas the binding to syntaxin N terminus plays a more limited role in neurosecretory cells.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Han L,Jiang T,Han GA,Malintan NT,Xie L,Wang L,Tse FW,Gaisano HY,Collins BM,Meunier FA,Sugita Sdoi
10.1091/mbc.e09-08-0712subject
Has Abstractpub_date
2009-12-01 00:00:00pages
4962-75issue
23eissn
1059-1524issn
1939-4586pii
E09-08-0712journal_volume
20pub_type
杂志文章abstract::Phospholipase D (PLD) has been suggested to mediate epidermal growth factor (EGF) signaling. However, the molecular mechanism of EGF-induced PLD activation has not yet been elucidated. We investigated the importance of the phosphorylation and compartmentalization of PLD1 in EGF signaling. EGF treatment of COS-7 cells ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-02-0100
更新日期:2002-11-01 00:00:00
abstract::Bile ducts are hepatic tubular structures that are lined by cholangiocytes, a type of liver epithelial cell. Cholangiocytes first form a single layer of cells, termed the ductal plate, surrounding the portal vein, which eventually remodels into the branching tubular network of bile ducts. The process of bile duct morp...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-02-0177
更新日期:2009-05-01 00:00:00
abstract::The proper execution of premeiotic S phase is essential to both the maintenance of genomic integrity and accurate chromosome segregation during the meiotic divisions. However, the regulation of premeiotic S phase remains poorly defined in metazoa. Here, we identify the p21(Cip1)/p27(Kip1)/p57(Kip2)-like cyclin-depende...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-09-0916
更新日期:2009-04-01 00:00:00
abstract::Cytoplasmic dynein is the major microtubule minus end-directed motor. Although studies have probed the mechanism of the C-terminal motor domain, if and how dynein's N-terminal tail and the accessory chains it binds regulate motor activity remain to be determined. Here, we investigate the structure and function of the ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-03-0166
更新日期:2013-08-01 00:00:00
abstract::Shiga-toxin-producing Escherichia coli remain a food-borne health threat. Shiga toxin is endocytosed by intestinal epithelial cells and transported retrogradely through the secretory pathway. It is ultimately translocated to the cytosol where it inhibits protein translation. We found that Shiga toxin transport through...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-02-0155
更新日期:2009-10-01 00:00:00
abstract::The secretory pathway along which newly synthesized secretory and membrane proteins traffic through the cell was revealed in two articles published 50 years ago. This discovery was the culmination of decades of effort to unite the power of biochemical and morphological methodologies in order to elucidate the dynamic n...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-07-0508
更新日期:2017-01-15 00:00:00
abstract::In the present study we have identified a new metalloprotease encoded by the nuclear ATP23 gene of Saccharomyces cerevisiae that is essential for expression of mitochondrial ATPase (F(1)-F(O) complex). Mutations in ATP23 cause the accumulation of the precursor form of subunit 6 and prevent assembly of F(O). Atp23p is ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-09-0801
更新日期:2007-02-01 00:00:00
abstract::Satellite cells (SCs), the resident adult stem cells of skeletal muscle, are required for tissue repair throughout life. While many signaling pathways are known to control SC self-renewal, less is known about the mechanisms underlying the spatiotemporal control of self-renewal during skeletal muscle repair. Here, we m...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E20-01-0078
更新日期:2020-07-21 00:00:00
abstract::The hypoxia-inducible factor (HIF) is a master regulator of the cellular response to hypoxia. Its levels and activity are controlled by dioxygenases called prolyl-hydroxylases and factor inhibiting HIF (FIH). To activate genes, HIF has to access sequences in DNA that are integrated in chromatin. It is known that the c...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-02-0163
更新日期:2011-11-01 00:00:00
abstract::Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linke...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-12-0932
更新日期:2011-07-01 00:00:00
abstract::The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.3.11.1259
更新日期:1992-11-01 00:00:00
abstract::Cdc42-associated tyrosine kinase 1 (ACK1) is a specific down-stream effector of Cdc42, a Rho family small G-protein. Previous studies have shown that ACK1 interacts with clathrin heavy chain and is involved in clathrin-coated vesicle endocytosis. Here we report that ACK1 interacted with epidermal growth factor recepto...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-02-0142
更新日期:2007-03-01 00:00:00
abstract::Emerging findings suggest that two lineages of mitochondrial Ca(2+) uptake participate during active and resting states: 1) the major eukaryotic membrane potential-dependent mitochondrial Ca(2+) uniporter and 2) the evolutionarily conserved exchangers and solute carriers, which are also involved in ion transport. Alth...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-08-0502
更新日期:2014-03-01 00:00:00
abstract::Werner syndrome (WS) is a human progeroid syndrome characterized by the early onset of a large number of clinical features associated with the normal aging process. The complex molecular and cellular phenotypes of WS involve characteristic features of genomic instability and accelerated replicative senescence. The gen...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.10.8.2655
更新日期:1999-08-01 00:00:00
abstract::In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated from βGlud1(-/-) mice ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-08-0676
更新日期:2012-10-01 00:00:00
abstract::Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implyi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.6.2069
更新日期:2000-06-01 00:00:00
abstract::Cilia serve as sensory devices in a diversity of organisms and their defects contribute to many human diseases. In primary cilia of kidney cells, the transient receptor potential polycystin (TRPP) channels polycystin-1 (PC-1) and polycystin-2 (PC-2) act as a mechanosensitive channel, with defects resulting in autosoma...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-10-0935
更新日期:2006-05-01 00:00:00
abstract::How nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. We previously reported that conventional protein kinase C (cPKC) contributes to nuclear size reductions that occur during early Xenopus development. Here we report that PKC-mediated p...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-11-0786
更新日期:2017-05-15 00:00:00
abstract::A number of peroxisome-associated proteins have been described that are involved in the import of proteins into peroxisomes, among which is the receptor for peroxisomal targeting signal 1 (PTS1) proteins Pex5p, the integral membrane protein Pex13p, which contains an Src homology 3 (SH3) domain, and the peripheral memb...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.11.3963
更新日期:2000-11-01 00:00:00
abstract::Motility of cilia (also known as flagella in some eukaryotes) is based on axonemal doublet microtubule sliding that is driven by the dynein molecular motors. Dyneins are organized into intricately patterned inner and outer rows of arms, whose collective activity is to produce inter-microtubule movement. However, to ge...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-07-0483
更新日期:2018-03-15 00:00:00
abstract::Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) and their counterreceptors such as intercellular cell adhesion molecules (ICAM-1 and ICAM-2), junctional adhesion molecules (JAM-A, JAM-C), and receptors for advanced glycation end products (RAGE) are crucial for promoting polymorphonucl...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-12-0827
更新日期:2018-02-15 00:00:00
abstract::ER quality control (ERQC) prevents the exit of misfolded secretory and membrane proteins from the ER. A critical aspect of ERQC is a transcriptional response called the unfolded protein response (UPR), which up-regulates genes that enable cells to cope with misfolded, ER-retained proteins. In this study, we compare th...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-02-0140
更新日期:2009-02-01 00:00:00
abstract::Although evasion of apoptosis is thought to be required for the development of cancer, it is unclear which cell death pathways are evaded. We previously identified a novel epithelial cell death pathway that works in normal cells but is inactivated in tumor cells, implying that it may be targeted during tumor developme...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-10-0906
更新日期:2005-03-01 00:00:00
abstract::Pif1 family helicases, which are found in nearly all eukaryotes, have important roles in both nuclear and mitochondrial genome maintenance. Recently, the increasing availability of genome sequences has revealed that Pif1 helicases are also widely found in diverse prokaryotes, but it is currently unknown what physiolog...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-01-0045
更新日期:2011-06-15 00:00:00
abstract::Dysregulated hepatic cholesterol homeostasis with free cholesterol accumulation in the liver is relevant to the pathogenesis of nonalcoholic steatohepatitis, contributing to the chronicity of liver toxicity. Here we examined the effect of free cholesterol accumulation on the morphology and biochemical properties of li...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-10-0730
更新日期:2016-11-01 00:00:00
abstract::We recently identified transmembrane protein shrew-1 and showed that it is able to target to adherens junctions in polarized epithelial cells. This suggested shrew-1 possesses specific basolateral sorting motifs, which we analyzed by mutational analysis. Systematic mutation of amino acids in putative sorting signals i...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-11-1034
更新日期:2006-08-01 00:00:00
abstract::The Notch signaling pathway plays essential roles in both animal development and human disease. Regulation of Notch receptor levels in membrane compartments has been shown to affect signaling in a variety of contexts. Here we used steady-state and pulse-labeling techniques to follow Notch receptors in sensory organ pr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-11-0751
更新日期:2016-09-15 00:00:00
abstract::We have identified and characterized sorb-1, the only sorbin and SH3 domain-containing protein family member in Caenorhabditis elegans SORB-1 is strongly localized to integrin adhesion complexes in larvae and adults, including adhesion plaques and dense bodies (Z-disks) of striated muscles and attachment plaques of sm...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-06-0455
更新日期:2017-12-01 00:00:00
abstract::Immunolocalization studies in epithelial cells revealed myo6 was associated with peripherally located vesicles that contained the transferrin receptor. Pulse-chase experiments after transferrin uptake showed that these vesicles were newly uncoated endocytic vesicles and that myo6 was recruited to these vesicles immedi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-11-0767
更新日期:2003-07-01 00:00:00
abstract::The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore pr...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-11-1560
更新日期:2015-05-15 00:00:00