Structure-based functional analysis reveals a role for the SM protein Sly1p in retrograde transport to the endoplasmic reticulum.

Abstract:

:Sec1p/Munc18 (SM) proteins are essential for membrane fusion events in eukaryotic cells. Here we describe a systematic, structure-based mutational analysis of the yeast SM protein Sly1p, which was previously shown to function in anterograde endoplasmic reticulum (ER)-to-Golgi and intra-Golgi protein transport. Five new temperature-sensitive (ts) mutants, each carrying a single amino acid substitution in Sly1p, were identified. Unexpectedly, not all of the ts mutants exhibited striking anterograde ER-to-Golgi transport defects. For example, in cells of the novel sly1-5 mutant, transport of newly synthesized lysosomal and secreted proteins was still efficient, but the ER-resident Kar2p/BiP was missorted to the outside of the cell, and two proteins, Sed5p and Rer1p, which normally shuttle between the Golgi and the ER, failed to relocate to the ER. We also discovered that in vivo, Sly1p was associated with a SNARE complex formed on the ER, and that in vitro, the SM protein directly interacted with the ER-localized nonsyntaxin SNAREs Use1p/Slt1p and Sec20p. Furthermore, several conditional mutants defective in Golgi-to-ER transport were synthetically lethal with sly1-5. Together, these results indicate a previously unrecognized function of Sly1p in retrograde transport to the endoplasmic reticulum.

journal_name

Mol Biol Cell

authors

Li Y,Gallwitz D,Peng R

doi

10.1091/mbc.e05-02-0114

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

3951-62

issue

9

eissn

1059-1524

issn

1939-4586

pii

E05-02-0114

journal_volume

16

pub_type

杂志文章
  • Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activity.

    abstract::The yeast SIR2 gene and many of its homologs have been identified as NAD(+)-dependent histone deacetylases. To get a broader view of the relationship between the histone deacetylase activity of Sir2p and its in vivo functions we have mutated eight highly conserved residues in the core domain of SIR2. These mutations h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-10-0482

    authors: Armstrong CM,Kaeberlein M,Imai SI,Guarente L

    更新日期:2002-04-01 00:00:00

  • The HOG pathway dictates the short-term translational response after hyperosmotic shock.

    abstract::Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-01-0006

    authors: Warringer J,Hult M,Regot S,Posas F,Sunnerhagen P

    更新日期:2010-09-01 00:00:00

  • The stem-loop binding protein (SLBP1) is present in coiled bodies of the Xenopus germinal vesicle.

    abstract::The stem-loop binding protein (SLBP1) binds the 3' stem-loop of histone pre-mRNA and is required for efficient processing of histone transcripts in the nucleus. We examined the localization of SLBP1 in the germinal vesicle of Xenopus laevis oocytes. In spread preparations of germinal vesicle contents, an anti-SLBP1 an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.2.487

    authors: Abbott J,Marzluff WF,Gall JG

    更新日期:1999-02-01 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

  • Apolipoprotein(a) stimulates nuclear translocation of β-catenin: a novel pathogenic mechanism for lipoprotein(a).

    abstract::Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease risk. This may be attributable to the ability of Lp(a) to elicit endothelial dysfunction. We previously reported that apolipoprotein(a) (apo(a); the distinguishing kringle-containing component of Lp(a)) elicits cytoskeletal rearrangements in vascular end...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-08-0637

    authors: Cho T,Romagnuolo R,Scipione C,Boffa MB,Koschinsky ML

    更新日期:2013-02-01 00:00:00

  • Temporary disruption of the plasma membrane is required for c-fos expression in response to mechanical stress.

    abstract::Mechanically stressed cells display increased levels of fos message and protein. Although the intracellular signaling pathways responsible for FOS induction have been extensively characterized, we still do not understand the nature of the primary cell mechanotransduction event responsible for converting an externally ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.4.1247

    authors: Grembowicz KP,Sprague D,McNeil PL

    更新日期:1999-04-01 00:00:00

  • Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control.

    abstract::Nuclear FGFR1 acts as a developmental gene regulator in cooperation with FGF-2, RSK1, and CREB-binding protein (CBP). FRAP analysis revealed three nuclear FGFR1 populations: i) a fast mobile, ii) a slower mobile population reflecting chromatin-bound FGFR1, and iii) an immobile FGFR1 population associated with the nucl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-06-0600

    authors: Dunham-Ems SM,Lee YW,Stachowiak EK,Pudavar H,Claus P,Prasad PN,Stachowiak MK

    更新日期:2009-05-01 00:00:00

  • Identification of integrin beta subunit mutations that alter heterodimer function in situ.

    abstract::We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila betaPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0085

    authors: Jannuzi AL,Bunch TA,West RF,Brower DL

    更新日期:2004-08-01 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

  • Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation.

    abstract::In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-11-0646

    authors: Willet AH,Bohnert KA,Gould KL

    更新日期:2018-03-15 00:00:00

  • Lectin-like Ox-LDL receptor is expressed in human INT-407 intestinal cells: involvement in the transcytosis of pancreatic bile salt-dependent lipase.

    abstract::We have recently shown that the pancreatic bile salt-dependent lipase (BSDL) can be taken up by intestinal cells and transported to the blood circulation. This mechanism likely involves (specific) receptor(s) able to bind BSDL and located at the apical intestinal cell membrane. In this study, using Int407 human intest...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-08-0544

    authors: Bruneau N,Richard S,Silvy F,Verine A,Lombardo D

    更新日期:2003-07-01 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

  • A member of the sugar transporter family, Stl1p is the glycerol/H+ symporter in Saccharomyces cerevisiae.

    abstract::Glycerol and other polyols are used as osmoprotectants by many organisms. Several yeasts and other fungi can take up glycerol by proton symport. To identify genes involved in active glycerol uptake in Saccharomyces cerevisiae we screened a deletion mutant collection comprising 321 genes encoding proteins with 6 or mor...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-10-0884

    authors: Ferreira C,van Voorst F,Martins A,Neves L,Oliveira R,Kielland-Brandt MC,Lucas C,Brandt A

    更新日期:2005-04-01 00:00:00

  • Identification of seven rat axonemal dynein heavy chain genes: expression during ciliated cell differentiation.

    abstract::Axonemal dyneins are molecular motors that drive the beating of cilia and flagella. We report here the identification and partial cloning of seven unique axonemal dynein heavy chains from rat tracheal epithelial (RTE) cells. Combinations of axonemal-specific and degenerate primers to conserved regions around the catal...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.7.1.71

    authors: Andrews KL,Nettesheim P,Asai DJ,Ostrowski LE

    更新日期:1996-01-01 00:00:00

  • Regulation of endocytosis, nuclear translocation, and signaling of fibroblast growth factor receptor 1 by E-cadherin.

    abstract::Fibroblast growth factor (FGF) receptors (FGFRs) signal to modulate diverse cellular functions, including epithelial cell morphogenesis. In epithelial cells, E-cadherin plays a key role in cell-cell adhesion, and its function can be regulated through endocytic trafficking. In this study, we investigated the location, ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-09-0845

    authors: Bryant DM,Wylie FG,Stow JL

    更新日期:2005-01-01 00:00:00

  • Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1.

    abstract::The mitochondrial cytochrome c oxidase assembles in the inner membrane from subunits of dual genetic origin. The assembly process of the enzyme is initiated by membrane insertion of the mitochondria-encoded Cox1 subunit. During complex maturation, transient assembly intermediates, consisting of structural subunits and...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-12-0811

    authors: Bareth B,Nikolov M,Lorenzi I,Hildenbeutel M,Mick DU,Helbig C,Urlaub H,Ott M,Rehling P,Dennerlein S

    更新日期:2016-05-15 00:00:00

  • Identification of a mitotic Rac-GEF, Trio, that counteracts MgcRacGAP function during cytokinesis.

    abstract::The Rho GTPases RhoA and Rac1 function as master regulators of cytokinesis by controlling the actomyosin cytoskeleton. RhoA and Rac1 have to be respectively activated and inactivated at the division plane for cytokinesis to occur properly. The inactivation of Rac1 at the cleavage furrow is controlled by MgcRacGAP. How...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1153

    authors: Cannet A,Schmidt S,Delaval B,Debant A

    更新日期:2014-12-15 00:00:00

  • Developmental expression of spectrins in rat skeletal muscle.

    abstract::Skeletal muscle contains spectrin (or spectrin I) and fodrin (or spectrin II), members of the spectrin supergene family. We used isoform-specific antibodies and cDNA probes to investigate the molecular forms, developmental expression, and subcellular localization of the spectrins in skeletal muscle of the rat. We repo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.1.47

    authors: Zhou D,Ursitti JA,Bloch RJ

    更新日期:1998-01-01 00:00:00

  • Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default.

    abstract::Select lipid-anchored proteins such as glycosylphosphatidylinositol (GPI)-anchored proteins and nonreceptor tyrosine kinases may preferentially partition into sphingomyelin-rich and cholesterol-rich plasmalemmal microdomains, thereby acquiring resistance to detergent extraction. Two such domains, caveolae and lipid ra...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.3.685

    authors: Oh P,Schnitzer JE

    更新日期:2001-03-01 00:00:00

  • Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression.

    abstract::Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-med...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-05-0364

    authors: Wang H,Wei E,Quiroga AD,Sun X,Touret N,Lehner R

    更新日期:2010-06-15 00:00:00

  • Golgi-associated cPLA2alpha regulates endothelial cell-cell junction integrity by controlling the trafficking of transmembrane junction proteins.

    abstract::In endothelial cells specifically, cPLA2alpha translocates from the cytoplasm to the Golgi complex in response to cell confluence. Considering the link between confluence and cell-cell junction formation, and the emerging role of cPLA2alpha in intracellular trafficking, we tested whether Golgi-associated cPLA2alpha is...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-02-0210

    authors: Regan-Klapisz E,Krouwer V,Langelaar-Makkinje M,Nallan L,Gelb M,Gerritsen H,Verkleij AJ,Post JA

    更新日期:2009-10-01 00:00:00

  • TRAF2 phosphorylation promotes NF-κB-dependent gene expression and inhibits oxidative stress-induced cell death.

    abstract::Tumor necrosis factor α (TNF-α) receptor-associated factor 2 (TRAF2) regulates activation of the c-Jun N-terminal kinase (JNK)/c-Jun and the inhibitor of κB kinase (IKK)/nuclear factor κB (NF-κB) signaling cascades in response to TNF-α stimulation. Gene knockout studies have revealed that TRAF2 inhibits TNF-α-induced ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-06-0556

    authors: Zhang L,Blackwell K,Altaeva A,Shi Z,Habelhah H

    更新日期:2011-01-01 00:00:00

  • Pol I transcription and pre-rRNA processing are coordinated in a transcription-dependent manner in mammalian cells.

    abstract::Pre-rRNA synthesis and processing are key steps in ribosome biogenesis. Although recent evidence in yeast suggests that these two processes are coupled, the nature of their association is unclear. In this report, we analyze the coordination between rDNA transcription and pre-rRNA processing in mammalian cells. We foun...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-03-0249

    authors: Kopp K,Gasiorowski JZ,Chen D,Gilmore R,Norton JT,Wang C,Leary DJ,Chan EK,Dean DA,Huang S

    更新日期:2007-02-01 00:00:00

  • Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis.

    abstract::The small G proteins Cdc42, Rac1, and Rac2 regulate the rearrangements of actin and membrane necessary for Fcgamma receptor-mediated phagocytosis by macrophages. Activated, GTP-bound Cdc42, Rac1, and Rac2 bind to the p21-binding domain (PBD) of PAK1, and this interaction provided a basis for microscopic methods to loc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-11-0847

    authors: Hoppe AD,Swanson JA

    更新日期:2004-08-01 00:00:00

  • Genetic interactions between the DBL-1/BMP-like pathway and dpy body size-associated genes in Caenorhabditis elegans.

    abstract::Bone morphogenetic protein (BMP) signaling pathways control many developmental and homeostatic processes, including cell size and extracellular matrix remodeling. An understanding of how this pathway itself is controlled remains incomplete. To identify novel regulators of BMP signaling, we performed a forward genetic ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-09-0500

    authors: Lakdawala MF,Madhu B,Faure L,Vora M,Padgett RW,Gumienny TL

    更新日期:2019-12-15 00:00:00

  • SNAP-23 regulates phagosome formation and maturation in macrophages.

    abstract::Synaptosomal associated protein of 23 kDa (SNAP-23), a plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), has been implicated in phagocytosis by macrophages. For elucidation of its precise role in this process, a macrophage line overexpressing monomeric Venus-tagge...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-01-0069

    authors: Sakurai C,Hashimoto H,Nakanishi H,Arai S,Wada Y,Sun-Wada GH,Wada I,Hatsuzawa K

    更新日期:2012-12-01 00:00:00

  • A p90(rsk) mutant constitutively interacting with MAP kinase uncouples MAP kinase from p34(cdc2)/cyclin B activation in Xenopus oocytes.

    abstract::The efficient activation of p90(rsk) by MAP kinase requires their interaction through a docking site located at the C-terminal end of p90(rsk). The MAP kinase p42(mpk1) can associate with p90(rsk) in G(2)-arrested but not in mature Xenopus oocytes. In contrast, an N-terminally truncated p90(rsk) mutant named D2 consti...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.9.2971

    authors: Gavin AC,Ni Ainle A,Chierici E,Jones M,Nebreda AR

    更新日期:1999-09-01 00:00:00

  • The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.

    abstract::The Arp2/3 complex is the only known nucleator of branched F-actin filaments. Work in cultured cells has established a wide array of functions for this complex in controlling cell migration, shape, and adhesion. However, loss of Arp2/3 complex function in tissues has yielded cell type-specific phenotypes. Here we repo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-10-1481

    authors: Zhou K,Sumigray KD,Lechler T

    更新日期:2015-06-01 00:00:00

  • Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles.

    abstract::Metaphase spindles assemble to a steady state in length by mechanisms that involve microtubule dynamics and motor proteins, but they are incompletely understood. We found that Xenopus extract spindles recapitulate the length of egg meiosis II spindles, by using mechanisms intrinsic to the spindle. To probe these mecha...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-02-0174

    authors: Mitchison TJ,Maddox P,Gaetz J,Groen A,Shirasu M,Desai A,Salmon ED,Kapoor TM

    更新日期:2005-06-01 00:00:00

  • The thrill of scientific discovery and leadership with my group.

    abstract::My group and I feel tremendously honored to be recognized with the 2016 Early Career Life Scientist Award from the American Society for Cell Biology. In this essay I share the scientific questions that my lab has been excitedly pursuing since starting in August 2009 and the leadership behaviors we have adopted that en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-06-0373

    authors: Greco V

    更新日期:2016-11-01 00:00:00