Vamp-7-dependent secretion at the immune synapse regulates antigen extraction and presentation in B-lymphocytes.

Abstract:

:Recognition of surface-tethered antigens (Ags) by B-cells leads to the formation of an immune synapse that promotes Ag uptake for presentation onto MHC-II molecules. Extraction of immobilized Ags at the immune synapse of B-cells relies on the local secretion of lysosomes, which are recruited to the Ag contact site by polarization of their microtubule network. Although conserved polarity proteins have been implicated in coordinating cytoskeleton remodeling with lysosome trafficking, the cellular machinery associated with lysosomal vesicles that regulates their docking and secretion at the synaptic interface has not been defined. Here we show that the v-SNARE protein Vamp-7 is associated with Lamp-1+ lysosomal vesicles, which are recruited and docked at the center of the immune synapse of B-cells. A decrease in Vamp-7 expression does not alter lysosome transport to the synaptic interface but impairs their local secretion, a defect that compromises the ability of B-cells to extract, process, and present immobilized Ag. Thus our results reveal that B-cells rely on the SNARE protein Vamp-7 to promote the local exocytosis of lysosomes at the immune synapse, which is required for efficient Ag extraction and presentation.

journal_name

Mol Biol Cell

authors

Obino D,Diaz J,Sáez JJ,Ibañez-Vega J,Sáez PJ,Alamo M,Lankar D,Yuseff MI

doi

10.1091/mbc.E16-10-0722

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

890-897

issue

7

eissn

1059-1524

issn

1939-4586

pii

mbc.E16-10-0722

journal_volume

28

pub_type

杂志文章
  • Fibronectin regulates assembly of actin filaments and focal contacts in cultured cells via the heparin-binding site in repeat III13.

    abstract::Fibroblasts, when plated on the extracellular matrix protein fibronectin (FN), rapidly spread and form an organized actin cytoskeleton. This process is known to involve both the central alpha5beta1 integrin-binding and the C-terminal heparin-binding regions of FN. We found that within the heparin-binding region, the i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.5.1521

    authors: Bloom L,Ingham KC,Hynes RO

    更新日期:1999-05-01 00:00:00

  • Differential regulation of distinct types of gap junction channels by similar phosphorylating conditions.

    abstract::Studies on physiological modulation of intercellular communication mediated by protein kinases are often complicated by the fact that cells express multiple gap junction proteins (connexins; Cx). Changes in cell coupling can be masked by simultaneous opposite regulation of the gap junction channel types expressed. We ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.12.1707

    authors: Kwak BR,Hermans MM,De Jonge HR,Lohmann SM,Jongsma HJ,Chanson M

    更新日期:1995-12-01 00:00:00

  • Functional cdc25C dual-specificity phosphatase is required for S-phase entry in human cells.

    abstract::In view of the common regulatory mechanism that induces transcription of the mitotic phosphatase cdc25C and cyclin A at the beginning of S-phase, we investigated whether cdc25C was required for S-phase transit. Here, we show that in both nontransformed human fibroblasts and HeLa cells, cdc25C protein levels significan...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-08-0515

    authors: Turowski P,Franckhauser C,Morris MC,Vaglio P,Fernandez A,Lamb NJ

    更新日期:2003-07-01 00:00:00

  • Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens.

    abstract::Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-01-0039

    authors: Ivkovic S,Beadle C,Noticewala S,Massey SC,Swanson KR,Toro LN,Bresnick AR,Canoll P,Rosenfeld SS

    更新日期:2012-02-01 00:00:00

  • Septins regulate junctional integrity of endothelial monolayers.

    abstract::Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions ext...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-02-0136

    authors: Kim J,Cooper JA

    更新日期:2018-07-15 00:00:00

  • p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation.

    abstract::The tumor suppressor protein p53 mediates stress-induced growth arrest or apoptosis and plays a major role in safeguarding genome integrity. In response to DNA damage, p53 can be modified at multiple sites by phosphorylation and acetylation. We report on the characterization of p53 C-terminal phosphorylation by CHK1 a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-08-0689

    authors: Ou YH,Chung PH,Sun TP,Shieh SY

    更新日期:2005-04-01 00:00:00

  • Swi5 controls a novel wave of cyclin synthesis in late mitosis.

    abstract::We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.4.945

    authors: Aerne BL,Johnson AL,Toyn JH,Johnston LH

    更新日期:1998-04-01 00:00:00

  • The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts.

    abstract::Podosomes are dynamic actin-rich structures composed of a dense F-actin core surrounded by a cloud of more diffuse F-actin. Src performs one or more unique functions in osteoclasts (OCLs), and podosome belts and bone resorption are impaired in the absence of Src. Using Src(-/-) OCLs, we investigated the specific funct...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-03-0227

    authors: Destaing O,Sanjay A,Itzstein C,Horne WC,Toomre D,De Camilli P,Baron R

    更新日期:2008-01-01 00:00:00

  • Tumor cell apoptosis polarizes macrophages role of sphingosine-1-phosphate.

    abstract::Macrophage polarization contributes to a number of human pathologies. This is exemplified for tumor-associated macrophages (TAMs), which display a polarized M2 phenotype, closely associated with promotion of angiogenesis and suppression of innate immune responses. We present evidence that induction of apoptosis in tum...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-12-1096

    authors: Weigert A,Tzieply N,von Knethen A,Johann AM,Schmidt H,Geisslinger G,Brüne B

    更新日期:2007-10-01 00:00:00

  • A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.

    abstract::We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.9.2829

    authors: Lee S,Parent CA,Insall R,Firtel RA

    更新日期:1999-09-01 00:00:00

  • Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.

    abstract::In the yeast Saccharomyces cerevisiae, the Apg12p-Apg5p conjugating system is essential for autophagy. Apg7p is required for the conjugation reaction, because Apg12p is unable to form a conjugate with Apg5p in the apg7/cvt2 mutant. Apg7p shows a significant similarity to a ubiquitin-activating enzyme, Uba1p. In this a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.10.5.1367

    authors: Tanida I,Mizushima N,Kiyooka M,Ohsumi M,Ueno T,Ohsumi Y,Kominami E

    更新日期:1999-05-01 00:00:00

  • Orientational order of the lamellipodial actin network as demonstrated in living motile cells.

    abstract::Lamellipodia of crawling cells represent both the motor for cell advance and the primary building site for the actin cytoskeleton. The organization of actin in the lamellipodium reflects actin dynamics and is of critical importance for the mechanism of cell motility. In previous structural studies, the lamellipodial a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-10-0630

    authors: Verkhovsky AB,Chaga OY,Schaub S,Svitkina TM,Meister JJ,Borisy GG

    更新日期:2003-11-01 00:00:00

  • RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity.

    abstract::The binding of extracellular matrix proteins to integrins triggers rearrangements in the actin cytoskeleton by regulating the Rho family of small GTPases. The signaling events that mediate changes in the activity of Rho proteins in response to the extracellular matrix remain largely unknown. We have demonstrated in pr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.9.2711

    authors: Arthur WT,Burridge K

    更新日期:2001-09-01 00:00:00

  • The putative G protein-coupled receptor GrlD mediates extracellular polyphosphate sensing in Dictyostelium discoideum.

    abstract::Five or more orthophosphates bound together by high-energy phosphoanhydride bonds are highly ubiquitous inorganic molecules called polyphosphate. Polyphosphate acts as a signaling molecule eliciting a number of responses in eukaryotic cells, but the mechanisms mediating these effects are poorly understood. Proliferati...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-10-0686

    authors: Suess PM,Tang Y,Gomer RH

    更新日期:2019-04-15 00:00:00

  • Down-regulation of the Wnt/β-catenin signaling pathway by Cacnb4.

    abstract::The β4 isoform of the β-subunits of voltage-gated calcium channel regulates cell proliferation and cell cycle progression. Herein we show that coexpression of the β4-subunit with actors of the canonical Wnt/β-catenin signaling pathway in a hepatoma cell line inhibits Wnt-responsive gene transcription and decreases cel...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-01-0076

    authors: Rima M,Daghsni M,Lopez A,Fajloun Z,Lefrancois L,Dunach M,Mori Y,Merle P,Brusés JL,De Waard M,Ronjat M

    更新日期:2017-12-01 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

  • The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin.

    abstract::MAGP-1 and fibrillin-1, two protein components of extracellular microfibrils, were shown by immunoprecipitation studies to interact with the chondroitin sulfate proteoglycan decorin in the medium of cultured fetal bovine chondrocytes. Decorin interacted with each protein individually and with both proteins together to...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.5.1499

    authors: Trask BC,Trask TM,Broekelmann T,Mecham RP

    更新日期:2000-05-01 00:00:00

  • Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu.

    abstract::Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15-20-fold up-regu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-06-0622

    authors: Andrew AJ,Song JY,Schilke B,Craig EA

    更新日期:2008-12-01 00:00:00

  • MyRIP interaction with MyoVa on secretory granules is controlled by the cAMP-PKA pathway.

    abstract::Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase A (PKA)-anchoring family, is implicated in hormone secretion. However, its mechanism of action is not fully elucidated. Here we investigate the role of MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transport and secretion in...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-05-0369

    authors: Brozzi F,Lajus S,Diraison F,Rajatileka S,Hayward K,Regazzi R,Molnár E,Váradi A

    更新日期:2012-11-01 00:00:00

  • Cross-linking CD98 promotes integrin-like signaling and anchorage-independent growth.

    abstract::CD98, an early marker of T-cell activation, is an important regulator of integrin-mediated adhesion events. Previous studies suggest that CD98 is coupled to both cellular activation and transformation and is involved in the pathogenesis of viral infection, inflammatory disease, and cancer. Understanding of the molecul...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-11-0530

    authors: Rintoul RC,Buttery RC,Mackinnon AC,Wong WS,Mosher D,Haslett C,Sethi T

    更新日期:2002-08-01 00:00:00

  • TOR and RAS pathways regulate desiccation tolerance in Saccharomyces cerevisiae.

    abstract::Tolerance to desiccation in cultures of Saccharomyces cerevisiae is inducible; only one in a million cells from an exponential culture survive desiccation compared with one in five cells in stationary phase. Here we exploit the desiccation sensitivity of exponentially dividing cells to understand the stresses imposed ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-07-0524

    authors: Welch AZ,Gibney PA,Botstein D,Koshland DE

    更新日期:2013-01-01 00:00:00

  • Fast-acting and nearly gratuitous induction of gene expression and protein depletion in Saccharomyces cerevisiae.

    abstract::We describe the development and characterization of a system that allows the rapid and specific induction of individual genes in the yeast Saccharomyces cerevisiae without changes in nutrients or temperature. The system is based on the chimeric transcriptional activator Gal4dbd.ER.VP16 (GEV). Upon addition of the horm...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-05-0466

    authors: McIsaac RS,Silverman SJ,McClean MN,Gibney PA,Macinskas J,Hickman MJ,Petti AA,Botstein D

    更新日期:2011-11-01 00:00:00

  • Protein arms in the kinetochore-microtubule interface of the yeast DASH complex.

    abstract::The yeast DASH complex is a heterodecameric component of the kinetochore necessary for accurate chromosome segregation. DASH forms closed rings around microtubules with a large gap between the DASH ring and the microtubule cylinder. We characterized the microtubule-binding properties of limited proteolysis products an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-02-0135

    authors: Miranda JJ,King DS,Harrison SC

    更新日期:2007-07-01 00:00:00

  • Control of lipid organization and actin assembly during clathrin-mediated endocytosis by the cytoplasmic tail of the rhomboid protein Rbd2.

    abstract::Clathrin-mediated endocytosis (CME) is facilitated by a precisely regulated burst of actin assembly. PtdIns(4,5)P2 is an important signaling lipid with conserved roles in CME and actin assembly regulation. Rhomboid family multipass transmembrane proteins regulate diverse cellular processes; however, rhomboid-mediated ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-11-1540

    authors: Cortesio CL,Lewellyn EB,Drubin DG

    更新日期:2015-04-15 00:00:00

  • Intrinsically active variants of Erk oncogenically transform cells and disclose unexpected autophosphorylation capability that is independent of TEY phosphorylation.

    abstract::The receptor-tyrosine kinase (RTK)/Ras/Raf pathway is an essential cascade for mediating growth factor signaling. It is abnormally overactive in almost all human cancers. The downstream targets of the pathway are members of the extracellular regulated kinases (Erk1/2) family, suggesting that this family is a mediator ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E15-07-0521

    authors: Smorodinsky-Atias K,Goshen-Lago T,Goldberg-Carp A,Melamed D,Shir A,Mooshayef N,Beenstock J,Karamansha Y,Darlyuk-Saadon I,Livnah O,Ahn NG,Admon A,Engelberg D

    更新日期:2016-03-15 00:00:00

  • Schizosaccharomyces pombe Pxl1 is a paxillin homologue that modulates Rho1 activity and participates in cytokinesis.

    abstract::Schizosaccharomyces pombe Rho GTPases regulate actin cytoskeleton organization and cell integrity. We studied the fission yeast gene SPBC4F6.12 based on its ability to suppress the thermosensitivity of cdc42-1625 mutant strain. This gene, named pxl1(+), encodes a protein with three LIM domains that is similar to paxil...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-07-0718

    authors: Pinar M,Coll PM,Rincón SA,Pérez P

    更新日期:2008-04-01 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

  • Retrograde Shiga toxin trafficking is regulated by ARHGAP21 and Cdc42.

    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

    authors: Hehnly H,Longhini KM,Chen JL,Stamnes M

    更新日期:2009-10-01 00:00:00

  • Cell polarity protein Spa2P associates with proteins involved in actin function in Saccharomyces cerevisiae.

    abstract::Spa2p is a nonessential protein that regulates yeast cell polarity. It localizes early to the presumptive bud site and remains at sites of growth throughout the cell cycle. To understand how Spa2p localization is regulated and to gain insight into its molecular function in cell polarity, we used a coimmunoprecipitatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-02-0108

    authors: Shih JL,Reck-Peterson SL,Newitt R,Mooseker MS,Aebersold R,Herskowitz I

    更新日期:2005-10-01 00:00:00

  • Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells.

    abstract::Griscelli syndrome type 2 (GS2) is a genetic disorder in which patients exhibit life-threatening defects of cytotoxic T lymphocytes (CTLs) whose lytic granules fail to dock on the plasma membrane and therefore do not release their contents. The disease is caused by the absence of functional rab27a, but how rab27a cont...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-10-0923

    authors: Neeft M,Wieffer M,de Jong AS,Negroiu G,Metz CH,van Loon A,Griffith J,Krijgsveld J,Wulffraat N,Koch H,Heck AJ,Brose N,Kleijmeer M,van der Sluijs P

    更新日期:2005-02-01 00:00:00