The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17.

Abstract:

:Membrane fusion is generally controlled by Rabs, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), and tethering complexes. Syntaxin 17 (STX17) was recently identified as the autophagosomal SNARE required for autophagosome-lysosome fusion in mammals and Drosophila. In this study, to better understand the mechanism of autophagosome-lysosome fusion, we searched for STX17-interacting proteins. Immunoprecipitation and mass spectrometry analysis identified vacuolar protein sorting 33A (VPS33A) and VPS16, which are components of the homotypic fusion and protein sorting (HOPS)-tethering complex. We further confirmed that all HOPS components were coprecipitated with STX17. Knockdown of VPS33A, VPS16, or VPS39 blocked autophagic flux and caused accumulation of STX17- and microtubule-associated protein light chain (LC3)-positive autophagosomes. The endocytic pathway was also affected by knockdown of VPS33A, as previously reported, but not by knockdown of STX17. By contrast, ultraviolet irradiation resistance-associated gene (UVRAG), a known HOPS-interacting protein, did not interact with the STX17-HOPS complex and may not be directly involved in autophagosome-lysosome fusion. Collectively these results suggest that, in addition to its well-established function in the endocytic pathway, HOPS promotes autophagosome-lysosome fusion through interaction with STX17.

journal_name

Mol Biol Cell

authors

Jiang P,Nishimura T,Sakamaki Y,Itakura E,Hatta T,Natsume T,Mizushima N

doi

10.1091/mbc.E13-08-0447

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

1327-37

issue

8

eissn

1059-1524

issn

1939-4586

pii

mbc.E13-08-0447

journal_volume

25

pub_type

杂志文章
  • Caenorhabditis elegans prom-1 is required for meiotic prophase progression and homologous chromosome pairing.

    abstract::A novel gene, prom-1, was isolated in a screen for Caenorhabditis elegans mutants with increased apoptosis in the germline. prom-1 encodes an F-box protein with limited homology to the putative human tumor suppressor FBXO47. Mutations in the prom-1 locus cause a strong reduction in bivalent formation, which results in...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-03-0243

    authors: Jantsch V,Tang L,Pasierbek P,Penkner A,Nayak S,Baudrimont A,Schedl T,Gartner A,Loidl J

    更新日期:2007-12-01 00:00:00

  • Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7.

    abstract::Timely degradation of regulatory proteins by the ubiquitin proteolytic pathway (UPP) is an established paradigm of cell cycle regulation during the G2/M and G1/S transitions. Less is known about roles for the UPP during S phase. Here we present evidence that dynamic cell cycle-dependent changes in levels of UbcH7 regu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-01-0036

    authors: Whitcomb EA,Dudek EJ,Liu Q,Taylor A

    更新日期:2009-01-01 00:00:00

  • Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells.

    abstract::Activation of the epidermal growth factor receptor (EGFR) triggers multiple signaling pathways and rapid endocytosis of the epidermal growth factor (EGF)-receptor complexes. To directly visualize the compartmentalization of molecules involved in the major signaling cascade, activation of Ras GTPase, we constructed fus...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-11-0552

    authors: Jiang X,Sorkin A

    更新日期:2002-05-01 00:00:00

  • Dual prenylation is required for Rab protein localization and function.

    abstract::The majority of Rab proteins are posttranslationally modified with two geranylgeranyl lipid moieties that enable their stable association with membranes. In this study, we present evidence to demonstrate that there is a specific lipid requirement for Rab protein localization and function. Substitution of different pre...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-11-0707

    authors: Calero M,Chen CZ,Zhu W,Winand N,Havas KA,Gilbert PM,Burd CG,Collins RN

    更新日期:2003-05-01 00:00:00

  • Association of 14-3-3 proteins to beta1-adrenergic receptors modulates Kv11.1 K+ channel activity in recombinant systems.

    abstract::We identify a new mechanism for the beta(1)-adrenergic receptor (beta(1)AR)-mediated regulation of human ether-a-go-go-related gene (HERG) potassium channel (Kv11.1). We find that the previously reported modulatory interaction between Kv11.1 channels and 14-3-3epsilon proteins is competed by wild type beta(1)AR by mea...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-05-0422

    authors: Tutor AS,Delpón E,Caballero R,Gómez R,Núñez L,Vaquero M,Tamargo J,Mayor F Jr,Penela P

    更新日期:2006-11-01 00:00:00

  • Morphogenesis in Kyoto: a confluence of cell and developmental biology.

    abstract::Understanding morphogenesis is the ultimate multidisciplinary (ad)venture. Three-dimensional tissues are generated from the actions of genes, biochemical pathways, and cells that form multicellular networks and interact with their biomechanical environment. A comprehensive explanation of morphogenetic processes must e...

    journal_title:Molecular biology of the cell

    pub_type:

    doi:10.1091/mbc.e09-12-1076

    authors: Zallen JA,Yap AS

    更新日期:2010-03-15 00:00:00

  • Chironomus tentans-repressor splicing factor represses SR protein function locally on pre-mRNA exons and is displaced at correct splice sites.

    abstract::Chironomus tentans-repressor splicing factor (Ct-RSF) represses the activation of splicing by SR proteins in vitro. Ct-RSF colocalizes with the Ser-Arg-rich (SR) protein hrp45 in interchromatin granule clusters and coimmunoprecipitates with hrp45 in nuclear extracts. Ct-RSF and hrp45 can also interact directly in vitr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-04-0339

    authors: Björk P,Wetterberg-Strandh I,Baurén G,Wieslander L

    更新日期:2006-01-01 00:00:00

  • Developing a set of guidelines for your research field: a practical approach.

    abstract::Since 2008, the autophagy community has periodically published a set of guidelines, currently titled "Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy." The newest version of the guidelines was published in 2016. There are many reasons for establishing a set of guidelines in a given researc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-09-0618

    authors: Klionsky DJ

    更新日期:2016-03-01 00:00:00

  • The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells.

    abstract::The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs....

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.9.3191

    authors: Mobarak CD,Anderson KD,Morin M,Beckel-Mitchener A,Rogers SL,Furneaux H,King P,Perrone-Bizzozero NI

    更新日期:2000-09-01 00:00:00

  • Cell type-dependent requirement for PIP box-regulated Cdt1 destruction during S phase.

    abstract::DNA synthesis-coupled proteolysis of the prereplicative complex component Cdt1 by the CRL4(Cdt2) E3 ubiquitin ligase is thought to help prevent rereplication of the genome during S phase. To directly test whether CRL4(Cdt2)-triggered destruction of Cdt1 is required for normal cell cycle progression in vivo, we express...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-02-0130

    authors: Lee HO,Zacharek SJ,Xiong Y,Duronio RJ

    更新日期:2010-11-01 00:00:00

  • Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein that controls host cell invasion.

    abstract::Cell invasion targets specific tissues in physiological placental implantation and pathological metastasis, which raises questions about how this process is controlled. We compare dermis and endometrium capacities to support trophoblast invasion, using matching sets of human primary fibroblasts in a coculture assay wi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-03-0142

    authors: Lopez-Mejia IC,De Toledo M,Della Seta F,Fafet P,Rebouissou C,Deleuze V,Blanchard JM,Jorgensen C,Tazi J,Vignais ML

    更新日期:2013-10-01 00:00:00

  • Galpha subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae.

    abstract::All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated Galpha subunit Gpa2 sense extracellular carbon sources (including glucose) to govern fila...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-05-0403

    authors: Harashima T,Heitman J

    更新日期:2005-10-01 00:00:00

  • Signal transduction by the platelet integrin alpha IIb beta 3: induction of calcium oscillations required for protein-tyrosine phosphorylation and ligand-induced spreading of stably transfected cells.

    abstract::We demonstrate an example of signal transduction by an integrin and have begun to define the pathway through which this signaling is achieved. We constructed a stably transfected derivative of 293 cells (ATCC 1573) that expresses the platelet integrin GPIIbIIIa (alpha IIb beta 3). This cell line, clone B, adheres to a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.9.989

    authors: Pelletier AJ,Bodary SC,Levinson AD

    更新日期:1992-09-01 00:00:00

  • Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge.

    abstract::Cell migration involves the cooperative reorganization of the actin and microtubule cytoskeletons, as well as the turnover of cell-substrate adhesions, under the control of Rho family GTPases. RhoA is activated at the leading edge of motile cells by unknown mechanisms to control actin stress fiber assembly, contractil...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-01-0041

    authors: Nalbant P,Chang YC,Birkenfeld J,Chang ZF,Bokoch GM

    更新日期:2009-09-01 00:00:00

  • Laminin 511 partners with laminin 332 to mediate directional migration of Madin-Darby canine kidney epithelial cells.

    abstract::Sustained directional migration of epithelial cells is essential for regeneration of injured epithelia. Front-rear polarity of migrating cells is determined by local activation of a signaling network involving Cdc42 and other factors in response to spatial cues from the environment, the nature of which are obscure. We...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-08-0718

    authors: Greciano PG,Moyano JV,Buschmann MM,Tang J,Lu Y,Rudnicki J,Manninen A,Matlin KS

    更新日期:2012-01-01 00:00:00

  • Lamin-dependent localization of UNC-84, a protein required for nuclear migration in Caenorhabditis elegans.

    abstract::Mutations in the Caenorhabditis elegans unc-84 gene cause defects in nuclear migration and anchoring. We show that endogenous UNC-84 protein colocalizes with Ce-lamin at the nuclear envelope and that the envelope localization of UNC-84 requires Ce-lamin. We also show that during mitosis, UNC-84 remains at the nuclear ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-06-0294

    authors: Lee KK,Starr D,Cohen M,Liu J,Han M,Wilson KL,Gruenbaum Y

    更新日期:2002-03-01 00:00:00

  • Polycystin-1 surface localization is stimulated by polycystin-2 and cleavage at the G protein-coupled receptor proteolytic site.

    abstract::Polycystin (PC)1 and PC2 are membrane proteins implicated in autosomal dominant polycystic kidney disease. A physiologically relevant cleavage at PC1's G protein-coupled receptor proteolytic site (GPS) occurs early in the secretory pathway. Our results suggest that PC2 increases both PC1 GPS cleavage and PC1's appeara...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-05-0407

    authors: Chapin HC,Rajendran V,Caplan MJ

    更新日期:2010-12-01 00:00:00

  • The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk uptake in Drosophila egg chambers.

    abstract::Clathrin-mediated endocytosis and phagocytosis are both selective surface internalization processes but have little known mechanistic similarity or interdependence. Here we show that the phosphotyrosine-binding (PTB) domain protein Ced-6, a well-established phagocytosis component that operates as a transducer of so-ca...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-11-0939

    authors: Jha A,Watkins SC,Traub LM

    更新日期:2012-05-01 00:00:00

  • Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level.

    abstract::During the course of a bacterial infection, cells are exposed simultaneously to a range of bacterial and host factors, which converge on the central transcription factor nuclear factor (NF)-κB. How do single cells integrate and process these converging stimuli? Here we tackle the question of how cells process combinat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-07-0423

    authors: Gutschow MV,Mason JC,Lane KM,Maayan I,Hughey JJ,Bajar BT,Amatya DN,Valle SD,Covert MW

    更新日期:2019-01-15 00:00:00

  • Effects of integrin-mediated cell adhesion on plasma membrane lipid raft components and signaling.

    abstract::Anchorage dependence of cell growth, which is mediated by multiple integrin-regulated signaling pathways, is a key defense against cancer metastasis. Detachment of cells from the extracellular matrix triggers caveolin-1-dependent internalization of lipid raft components, which mediates suppression of Rho GTPases, Erk,...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-04-0361

    authors: Norambuena A,Schwartz MA

    更新日期:2011-09-01 00:00:00

  • A double-strand break repair component is essential for S phase completion in fission yeast cell cycling.

    abstract::Fission yeast rad22(+), a homologue of budding yeast RAD52, encodes a double-strand break repair component, which is dispensable for proliferation. We, however, have recently obtained a cell division cycle mutant with a temperature-sensitive allele of rad22(+), designated rad22-H6, which resulted from a point mutation...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.10.3331

    authors: Suto K,Nagata A,Murakami H,Okayama H

    更新日期:1999-10-01 00:00:00

  • Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation.

    abstract::The nucleus houses, organizes, and protects chromatin to ensure genome integrity and proper gene expression, but how the nucleus adapts mechanically to changes in the extracellular environment is poorly understood. Recent studies have revealed that extracellular physical stresses induce chromatin compaction via mechan...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-05-0286-T

    authors: Stephens AD,Liu PZ,Kandula V,Chen H,Almassalha LM,Herman C,Backman V,O'Halloran T,Adam SA,Goldman RD,Banigan EJ,Marko JF

    更新日期:2019-06-19 00:00:00

  • Analysis of the roles of phosphatidylinositol-4,5-bisphosphate and individual subunits in assembly, localization, and function of Saccharomyces cerevisiae target of rapamycin complex 2.

    abstract::Eukaryotic cell survival requires maintenance of plasma membrane (PM) homeostasis in response to environmental insults and changes in lipid metabolism. In yeast, a key regulator of PM homeostasis is target of rapamycin (TOR) complex 2 (TORC2), a multiprotein complex containing the evolutionarily conserved TOR protein ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-10-0682

    authors: Martinez Marshall MN,Emmerstorfer-Augustin A,Leskoske KL,Zhang LH,Li B,Thorner J

    更新日期:2019-06-01 00:00:00

  • Selective protein exit from yeast endoplasmic reticulum in absence of functional COPII coat component Sec13p.

    abstract::Sec13p has been thought to be an essential component of the COPII coat, required for exit of proteins from the yeast endoplasmic reticulum (ER). We show herein that normal function of Sec13p was not required for ER exit of the Hsp150 glycoprotein. Hsp150 was secreted to the medium under restrictive conditions in a sec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.02-05-0082

    authors: Fatal N,Suntio T,Makarow M

    更新日期:2002-12-01 00:00:00

  • Clustering and lateral concentration of raft lipids by the MAL protein.

    abstract::MAL, a compact hydrophobic, four-transmembrane-domain apical protein that copurifies with detergent-resistant membranes is obligatory for the machinery that sorts glycophosphatidylinositol (GPI)-anchored proteins and others to the apical membrane in epithelia. The mechanism of MAL function in lipid-raft-mediated apica...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-02-0142

    authors: Magal LG,Yaffe Y,Shepshelovich J,Aranda JF,de Marco Mdel C,Gaus K,Alonso MA,Hirschberg K

    更新日期:2009-08-01 00:00:00

  • Cyclic GMP-specific phosphodiesterase-5 regulates motility of sea urchin spermatozoa.

    abstract::Motility, chemotaxis, and the acrosome reaction of animal sperm are all regulated by cyclic nucleotides and protein phosphorylation. One of the cyclic AMP-dependent protein kinase (PKA) substrates in sea urchin sperm is a member of the phosphodiesterase (PDE) family. The molecular identity and in vivo function of this...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-08-0820

    authors: Su YH,Vacquier VD

    更新日期:2006-01-01 00:00:00

  • Myosin IIC: a third molecular motor driving neuronal dynamics.

    abstract::Neuronal dynamics result from the integration of forces developed by molecular motors, especially conventional myosins. Myosin IIC is a recently discovered nonsarcomeric conventional myosin motor, the function of which is poorly understood, particularly in relation to the separate but coupled activities of its close h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-08-0744

    authors: Wylie SR,Chantler PD

    更新日期:2008-09-01 00:00:00

  • Defined spatiotemporal features of RAS-ERK signals dictate cell fate in MCF-7 mammary epithelial cells.

    abstract::Signals conveyed through the RAS-ERK pathway are essential for the determination of cell fate. It is well established that signal variability is achieved in the different microenvironments in which signals unfold. It is also known that signal duration is critical for decisions concerning cell commitment. However, it i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-02-0118

    authors: Herrero A,Casar B,Colón-Bolea P,Agudo-Ibáñez L,Crespo P

    更新日期:2016-06-15 00:00:00

  • A secreted MMP is required for reepithelialization during wound healing.

    abstract::Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaste...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-09-0745

    authors: Stevens LJ,Page-McCaw A

    更新日期:2012-03-01 00:00:00

  • Dynein-dependent motility of microtubules and nucleation sites supports polarization of the tubulin array in the fungus Ustilago maydis.

    abstract::Microtubules (MTs) are often organized by a nucleus-associated MT organizing center (MTOC). In addition, in neurons and epithelial cells, motor-based transport of assembled MTs determines the polarity of the MT array. Here, we show that MT motility participates in MT organization in the fungus Ustilago maydis. In budd...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-12-1118

    authors: Fink G,Steinberg G

    更新日期:2006-07-01 00:00:00