Phosphorylation of the effector complex HOPS by the vacuolar kinase Yck3p confers Rab nucleotide specificity for vacuole docking and fusion.

Abstract:

:The homotypic fusion of yeast vacuoles requires the Rab-family GTPase Ypt7p and its effector complex, homotypic fusion and vacuole protein sorting complex (HOPS). Although the vacuolar kinase Yck3p is required for the sensitivity of vacuole fusion to proteins that regulate the Rab GTPase cycle-Gdi1p (GDP-dissociation inhibitor [GDI]) or Gyp1p/Gyp7p (GTPase-activating protein)-this kinase phosphorylates HOPS rather than Ypt7p. We addressed this puzzle in reconstituted proteoliposome fusion reactions with all-purified components. In the presence of HOPS and Sec17p/Sec18p, there is comparable fusion of 4-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteoliposomes when they have Ypt7p bearing either GDP or GTP, a striking exception to the rule that only GTP-bound forms of Ras-superfamily GTPases have active conformations. However, the phosphorylation of HOPS by recombinant Yck3p confers a strict requirement for GTP-bound Ypt7p for binding phosphorylated HOPS, for optimal membrane tethering, and for proteoliposome fusion. Added GTPase-activating protein promotes GTP hydrolysis by Ypt7p, and added GDI captures Ypt7p in its GDP-bound state during nucleotide cycling. In either case, the net conversion of Ypt7:GTP to Ypt7:GDP has no effect on HOPS binding or activity but blocks fusion mediated by phosphorylated HOPS. Thus guanine nucleotide specificity of the vacuolar fusion Rab Ypt7p is conferred through downstream posttranslational modification of its effector complex.

journal_name

Mol Biol Cell

authors

Zick M,Wickner W

doi

10.1091/mbc.E12-04-0279

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

3429-37

issue

17

eissn

1059-1524

issn

1939-4586

pii

mbc.E12-04-0279

journal_volume

23

pub_type

杂志文章
  • Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding.

    abstract::14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-12-0821

    authors: Shen YH,Godlewski J,Bronisz A,Zhu J,Comb MJ,Avruch J,Tzivion G

    更新日期:2003-11-01 00:00:00

  • CD1 and major histocompatibility complex II molecules follow a different course during dendritic cell maturation.

    abstract::The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that medi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-11-0744

    authors: van der Wel NN,Sugita M,Fluitsma DM,Cao X,Schreibelt G,Brenner MB,Peters PJ

    更新日期:2003-08-01 00:00:00

  • Plasma membrane organization and function: moving past lipid rafts.

    abstract::"Lipid raft" is the name given to the tiny, dynamic, and ordered domains of cholesterol and sphingolipids that are hypothesized to exist in the plasma membranes of eukaryotic cells. According to the lipid raft hypothesis, these cholesterol- and sphingolipid-enriched domains modulate the protein-protein interactions th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-03-0165

    authors: Kraft ML

    更新日期:2013-09-01 00:00:00

  • Alpha5beta1 integrin controls cyclin D1 expression by sustaining mitogen-activated protein kinase activity in growth factor-treated cells.

    abstract::Cyclin D1 expression is jointly regulated by growth factors and cell adhesion to the extracellular matrix in many cell types. Growth factors are thought to regulate cyclin D1 expression because they stimulate sustained extracellular signal-regulated kinase (ERK) activity. However, we show here that growth factors indu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.10.3197

    authors: Roovers K,Davey G,Zhu X,Bottazzi ME,Assoian RK

    更新日期:1999-10-01 00:00:00

  • Dynamic association of the PI3P-interacting Mon1-Ccz1 GEF with vacuoles is controlled through its phosphorylation by the type 1 casein kinase Yck3.

    abstract::Maturation of organelles in the endolysosomal pathway requires exchange of the early endosomal GTPase Rab5/Vps21 for the late endosomal Rab7/Ypt7. The Rab exchange depends on the guanine nucleotide exchange factor activity of the Mon1-Ccz1 heterodimer for Ypt7. Here we investigate vacuole binding and recycling of Mon1...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0460

    authors: Lawrence G,Brown CC,Flood BA,Karunakaran S,Cabrera M,Nordmann M,Ungermann C,Fratti RA

    更新日期:2014-05-01 00:00:00

  • ISWI remodeling complexes in Xenopus egg extracts: identification as major chromosomal components that are regulated by INCENP-aurora B.

    abstract::We previously characterized major components of mitotic chromosomes assembled in Xenopus laevis egg extracts and collectively referred to them as Xenopus chromosome-associated polypeptides (XCAPs). They included five subunits of the condensin complex essential for chromosome condensation. In an effort to identify nove...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-09-0441

    authors: MacCallum DE,Losada A,Kobayashi R,Hirano T

    更新日期:2002-01-01 00:00:00

  • The RHO1-specific GTPase-activating protein LRG1 regulates polar tip growth in parallel to Ndr kinase signaling in Neurospora.

    abstract::Regulation of Rho GTPase signaling is critical for cell shape determination and polarity. Here, we investigated the role of LRG1, a novel member of the GTPase-activating proteins (GAPs) of Neurospora crassa. LRG1 is essential for apical tip extension and to restrict excessive branch formation in subapical regions of t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-12-1266

    authors: Vogt N,Seiler S

    更新日期:2008-11-01 00:00:00

  • The SNAP-25 linker as an adaptation toward fast exocytosis.

    abstract::The assembly of four soluble N-ethylmaleimide-sensitive factor attachment protein receptor domains into a complex is essential for membrane fusion. In most cases, the four SNARE-domains are encoded by separate membrane-targeted proteins. However, in the exocytotic pathway, two SNARE-domains are present in one protein,...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-12-1218

    authors: Nagy G,Milosevic I,Mohrmann R,Wiederhold K,Walter AM,Sørensen JB

    更新日期:2008-09-01 00:00:00

  • Gene expression patterns in human liver cancers.

    abstract::Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily di...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.02-02-0023

    authors: Chen X,Cheung ST,So S,Fan ST,Barry C,Higgins J,Lai KM,Ji J,Dudoit S,Ng IO,Van De Rijn M,Botstein D,Brown PO

    更新日期:2002-06-01 00:00:00

  • Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects.

    abstract::Endoplasmic reticulum-localized DnaJ 4 (ERdj4) is an immunoglobulin-binding protein (BiP) cochaperone and component of the endoplasmic reticulum-associated degradation (ERAD) pathway that functions to remove unfolded/misfolded substrates from the ER lumen under conditions of ER stress. To elucidate the function of ERd...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-06-0319

    authors: Fritz JM,Dong M,Apsley KS,Martin EP,Na CL,Sitaraman S,Weaver TE

    更新日期:2014-02-01 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

  • 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

  • Translational suppression of syndecan-1 expression in Ha-ras transformed mouse mammary epithelial cells.

    abstract::A cell surface proteoglycan, syndecan-1, has been shown to participate in the maintenance of the epithelial cell morphology. A point mutated activated c-Ha-ras gene under the control of the glucocorticoid inducible MMTV-LTR promoter was transfected into the mouse mammary epithelial cell line, NOG-8. The NOG-8 ras cell...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.4.8.849

    authors: Kirjavainen J,Leppä S,Hynes NE,Jalkanen M

    更新日期:1993-08-01 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

  • The same receptor, G protein, and mitogen-activated protein kinase pathway activate different downstream regulators in the alternative white and opaque pheromone responses of Candida albicans.

    abstract::Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-07-0688

    authors: Yi S,Sahni N,Daniels KJ,Pujol C,Srikantha T,Soll DR

    更新日期:2008-03-01 00:00:00

  • Maloriented bivalents have metaphase positions at the spindle equator with more kinetochore microtubules to one pole than to the other.

    abstract::To test the "traction fiber" model for metaphase positioning of bivalents during meiosis, kinetochore fibers of maloriented bivalents, induced during recovery from cold arrest, were analyzed with a liquid crystal polarizing microscope. The measured birefringence retardation of kinetochore fibers is proportional to the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-06-0524

    authors: LaFountain JR Jr,Oldenbourg R

    更新日期:2004-12-01 00:00:00

  • Reorganization of budding yeast cytoplasm upon energy depletion.

    abstract::Yeast cells, when exposed to stress, can enter a protective state in which cell division, growth, and metabolism are down-regulated. They remain viable in this state until nutrients become available again. How cells enter this protective survival state and what happens at a cellular and subcellular level are largely u...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-02-0125

    authors: Marini G,Nüske E,Leng W,Alberti S,Pigino G

    更新日期:2020-06-01 00:00:00

  • A statistical anomaly indicates symbiotic origins of eukaryotic membranes.

    abstract::Compositional analyses of nucleic acids and proteins have shed light on possible origins of living cells. In this work, rigorous compositional analyses of ∼5000 plasma membrane lipid constituents of 273 species in the three life domains (archaea, eubacteria, and eukaryotes) revealed a remarkable statistical paradox, i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1078

    authors: Bansal S,Mittal A

    更新日期:2015-04-01 00:00:00

  • Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.

    abstract::Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.10.1333

    authors: Campbell SD,Sprenger F,Edgar BA,O'Farrell PH

    更新日期:1995-10-01 00:00:00

  • Down-regulation of cell surface receptors is modulated by polar residues within the transmembrane domain.

    abstract::How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.8.2643

    authors: Zaliauskiene L,Kang S,Brouillette CG,Lebowitz J,Arani RB,Collawn JF

    更新日期:2000-08-01 00:00:00

  • In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins.

    abstract::The intermembrane space of mitochondria accommodates the essential mitochondrial intermembrane space assembly (MIA) machinery that catalyzes oxidative folding of proteins. The disulfide bond formation pathway is based on a relay of reactions involving disulfide transfer from the sulfhydryl oxidase Erv1 to Mia40 and fr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-05-0358

    authors: Böttinger L,Gornicka A,Czerwik T,Bragoszewski P,Loniewska-Lwowska A,Schulze-Specking A,Truscott KN,Guiard B,Milenkovic D,Chacinska A

    更新日期:2012-10-01 00:00:00

  • SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors.

    abstract::SINC, a new type III secreted protein of the avian and human pathogen Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci-infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of SINC-GFP-transfected HeLa cells indicate that SINC targets the inner nuclear membrane. SI...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-11-1530

    authors: Mojica SA,Hovis KM,Frieman MB,Tran B,Hsia RC,Ravel J,Jenkins-Houk C,Wilson KL,Bavoil PM

    更新日期:2015-05-15 00:00:00

  • Environmental transition of signal-anchor sequences during membrane insertion via the endoplasmic reticulum translocon.

    abstract::In biogenesis of membrane proteins on the endoplasmic reticulum, a protein-conducting channel called the translocon functions in both the membrane translocation of lumenal domains and the integration of transmembrane segments. Here we analyzed the environments of polypeptide chains during the processes by water-depend...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0738

    authors: Kida Y,Kume C,Hirano M,Sakaguchi M

    更新日期:2010-02-01 00:00:00

  • In vitro assembly of coiled bodies in Xenopus egg extract.

    abstract::When demembranated sperm nuclei are placed in a Xenopus egg extract, they become surrounded by a nuclear envelope and then swell to form morphologically typical pronuclei. Granules ranging from < 1.0 to approximately 3.0 microns in diameter appear within such nuclei. Bell et al. identified four nucleolar proteins in t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.5.6.633

    authors: Bauer DW,Murphy C,Wu Z,Wu CH,Gall JG

    更新日期:1994-06-01 00:00:00

  • Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration.

    abstract::The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions di...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0506

    authors: Bernis C,Swift-Taylor B,Nord M,Carmona S,Chook YM,Forbes DJ

    更新日期:2014-04-01 00:00:00

  • Dissociation of the Nuf2-Ndc80 complex releases centromeres from the spindle-pole body during meiotic prophase in fission yeast.

    abstract::In the fission yeast Schizosaccharomyces pombe, centromeres remain clustered at the spindle-pole body (SPB) during mitotic interphase. In contrast, during meiotic prophase centromeres dissociate from the SPB. Here we examined the behavior of centromere proteins in living meiotic cells of S. pombe. We show that the Nuf...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-11-0996

    authors: Asakawa H,Hayashi A,Haraguchi T,Hiraoka Y

    更新日期:2005-05-01 00:00:00

  • Direct binding to Rsp5 mediates ubiquitin-independent sorting of Sna3 via the multivesicular body pathway.

    abstract::The sorting of most integral membrane proteins into the lumenal vesicles of multivesicular bodies (MVBs) is dependent on the attachment of ubiquitin (Ub) to their cytosolic domains. However, Ub is not required for sorting of Sna3, an MVB vesicle cargo protein in yeast. We show that Sna3 circumvents Ub-mediated recogni...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-08-0663

    authors: McNatt MW,McKittrick I,West M,Odorizzi G

    更新日期:2007-02-01 00:00:00

  • Rescue of Munc18-1 and -2 double knockdown reveals the essential functions of interaction between Munc18 and closed syntaxin in PC12 cells.

    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 prec...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-08-0712

    authors: Han L,Jiang T,Han GA,Malintan NT,Xie L,Wang L,Tse FW,Gaisano HY,Collins BM,Meunier FA,Sugita S

    更新日期:2009-12-01 00:00:00

  • Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress.

    abstract::In Schizosaccharomyces pombe, the Sty1 mitogen-activated protein kinase and the Atf1 transcription factor control transcriptional induction in response to elevated salt concentrations. Herein, we demonstrate that two repressors, Tup11 and Tup12, and the Prr1 transcription factor also function in the response to salt s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-12-0568

    authors: Greenall A,Hadcroft AP,Malakasi P,Jones N,Morgan BA,Hoffman CS,Whitehall SK

    更新日期:2002-09-01 00:00:00

  • Phosphorylation of Serine 114 on Atg32 mediates mitophagy.

    abstract::Mitophagy, which selectively degrades mitochondria via autophagy, has a significant role in mitochondrial quality control. When mitophagy is induced in yeast, mitochondrial residential protein Atg32 binds Atg11, an adaptor protein for selective types of autophagy, and it is recruited into the vacuole along with mitoch...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-02-0145

    authors: Aoki Y,Kanki T,Hirota Y,Kurihara Y,Saigusa T,Uchiumi T,Kang D

    更新日期:2011-09-01 00:00:00