Gene Symbol: Stx4a
Description: syntaxin 4A (placental)
Alias: Stx4, Syn-4, Syn4, syntaxin-4
Species: mouse
Products:     Stx4a

Top Publications

  1. Gangar A, Rossi G, Andreeva A, Hales R, Brennwald P. Structurally conserved interaction of Lgl family with SNAREs is critical to their cellular function. Curr Biol. 2005;15:1136-42 pubmed
    ..These data support the model that the Lgl family functions in cell polarity, at least in part, by regulating SNARE-mediated membrane delivery events at the cell surface. ..
  2. Tellam J, Macaulay S, McIntosh S, Hewish D, Ward C, James D. Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4. J Biol Chem. 1997;272:6179-86 pubmed
    ..These data suggest that syntaxin-4/Munc-18c/VAMP-2 may play a role in the docking/fusion of intracellular GLUT-4-containing vesicles with the cell surface in adipocytes. ..
  3. Wang C, Ng C, Lu L, Atlashkin V, Zhang W, Seet L, et al. A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells. Dev Cell. 2004;7:359-71 pubmed
    ..VAMP8 is enriched on the membrane of zymogen granules and exists in a complex with syntaxin 4 and SNAP-23. VAMP8-/- mice developed normally but showed severe defects in the pancreas...
  4. Hu S, Latham C, Gee C, James D, Martin J. Structure of the Munc18c/Syntaxin4 N-peptide complex defines universal features of the N-peptide binding mode of Sec1/Munc18 proteins. Proc Natl Acad Sci U S A. 2007;104:8773-8 pubmed
    ..The mammalian cell surface SM protein Munc18c binds to an N-peptide in Stx4, and this is compatible with its interaction with SNARE complexes...
  5. Kanda H, Tamori Y, Shinoda H, Yoshikawa M, Sakaue M, Udagawa J, et al. Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization. J Clin Invest. 2005;115:291-301 pubmed
  6. Spurlin B, Park S, Nevins A, Kim J, Thurmond D. Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. Diabetes. 2004;53:2223-31 pubmed
    ..vesicles from an intracellular compartment to the plasma membrane in 3T3L1 adipocytes is mediated through a syntaxin 4 (Syn4)- and Munc18c-dependent mechanism...
  7. Widberg C, Bryant N, Girotti M, Rea S, James D. Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation. J Biol Chem. 2003;278:35093-101 pubmed
    ..These data suggest that Tomosyn and Munc18c operate at a similar stage of the Syntaxin4 SNARE assembly cycle, which likely primes Syntaxin4 for entry into the ternary SNARE complex. ..
  8. Procino G, Barbieri C, Tamma G, De Benedictis L, Pessin J, Svelto M, et al. AQP2 exocytosis in the renal collecting duct -- involvement of SNARE isoforms and the regulatory role of Munc18b. J Cell Sci. 2008;121:2097-106 pubmed publisher
  9. Jewell J, Oh E, Bennett S, Meroueh S, Thurmond D. The tyrosine phosphorylation of Munc18c induces a switch in binding specificity from syntaxin 4 to Doc2beta. J Biol Chem. 2008;283:21734-46 pubmed publisher
    Glucose-stimulated insulin secretion is mediated by syntaxin 4-based SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes and the Sec1/Munc18 protein Munc18c...

Scientific Experts

More Information


  1. Ke B, Oh E, Thurmond D. Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin 4-mediated exocytosis. J Biol Chem. 2007;282:21786-97 pubmed
    ..Although Munc18c function is known to involve binding to the t-SNARE Syntaxin 4, a paucity of Munc18c-binding proteins has restricted elucidation of the mechanism by which it facilitates these ..
  2. Latham C, Lopez J, Hu S, Gee C, Westbury E, Blair D, et al. Molecular dissection of the Munc18c/syntaxin4 interaction: implications for regulation of membrane trafficking. Traffic. 2006;7:1408-19 pubmed
    ..The Munc18c-SNARE interactions described here imply that Munc18c could play a positive regulatory role in SNARE assembly. ..
  3. Spurlin B, Thurmond D. Syntaxin 4 facilitates biphasic glucose-stimulated insulin secretion from pancreatic beta-cells. Mol Endocrinol. 2006;20:183-93 pubmed
    Numerous overexpression studies have recently implicated Syntaxin 4 as an effector of insulin secretion, although its requirement in insulin granule exocytosis is unknown...
  4. Yang C, Coker K, Kim J, Mora S, Thurmond D, Davis A, et al. Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. J Clin Invest. 2001;107:1311-8 pubmed
    To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice...
  5. Jurado S, Goswami D, Zhang Y, Molina A, Sudhof T, Malenka R. LTP requires a unique postsynaptic SNARE fusion machinery. Neuron. 2013;77:542-58 pubmed publisher
    ..Thus, postsynaptic exocytosis of AMPARs during LTP is mediated by a unique fusion machinery that is distinct from that used during presynaptic neurotransmitter release. ..
  6. Hu S, Christie M, Saez N, Latham C, Jarrott R, Lua L, et al. Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation. Proc Natl Acad Sci U S A. 2011;108:1040-5 pubmed publisher
    ..We hypothesize that Munc18-1 domain 3a undergoes a conformational change that may allow coiled-coil interactions with SNARE complexes. ..
  7. Tian W, Ma C, Liu Y, Xu T. An efficient co-expression and purification system for the complex of Stx4 and C-terminal domain of Synip. Biochem Biophys Res Commun. 2008;371:366-70 pubmed publisher
    Synip and Stx4 complex plays a key role in GLUT4 vesicle trafficking and fusion with plasma membrane. The interaction of Synip with Stx4 prevents interaction of VAMP2 located in GLUT4 vesicle with Stx4 in basal state...
  8. Jewell J, Oh E, Thurmond D. Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4. Am J Physiol Regul Integr Comp Physiol. 2010;298:R517-31 pubmed publisher
    ..Munc18-syntaxin isoform pairs, whereas insulin action in the peripheral tissues appears to use only the Munc18c-syntaxin 4 pair...
  9. Kalwat M, Wiseman D, Luo W, Wang Z, Thurmond D. Gelsolin associates with the N terminus of syntaxin 4 to regulate insulin granule exocytosis. Mol Endocrinol. 2012;26:128-41 pubmed publisher
    ..In a screen to identify new Syn4-interacting factors, the calcium-activated F-actin-severing protein gelsolin was revealed...
  10. Ozcelik M, Cotter L, Jacob C, Pereira J, Relvas J, Suter U, et al. Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves. J Neurosci. 2010;30:4120-31 pubmed publisher
    ..We conclude that regulation of epithelial-like polarization is a critical determinant of myelin sheath structure and function. ..
  11. Kawai S, Michikami I, Kitagaki J, Hata K, Kiyonari H, Abe T, et al. Syntaxin 4a Regulates Matrix Vesicle-Mediated Bone Matrix Production by Osteoblasts. J Bone Miner Res. 2017;32:440-448 pubmed publisher
    ..factor (NSF) attachment protein receptor" (SNARE) genes and identified notable Syntaxin 4a (Stx4a) expression on the basolateral side of the plasma membrane of osteoblasts...
  12. Ye S, Karim Z, Al Hawas R, Pessin J, Filipovich A, Whiteheart S. Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion. Blood. 2012;120:2484-92 pubmed
    ..The results of the present study indicate that syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet exocytosis. ..
  13. Müsch A, Cohen D, Yeaman C, Nelson W, Rodriguez Boulan E, Brennwald P. Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae interacts with basolateral exocytic machinery in Madin-Darby canine kidney cells. Mol Biol Cell. 2002;13:158-68 pubmed
    ..Membrane-bound Mlgl from MDCK cell lysates was coimmunoprecipitated with syntaxin 4, a component of the exocytic machinery at the basolateral membrane, but not with other plasma membrane soluble N-..
  14. Wade N, Bryant N, Connolly L, Simpson R, Luzio J, Piper R, et al. Syntaxin 7 complexes with mouse Vps10p tail interactor 1b, syntaxin 6, vesicle-associated membrane protein (VAMP)8, and VAMP7 in b16 melanoma cells. J Biol Chem. 2001;276:19820-7 pubmed
  15. Kawaguchi T, Tamori Y, Kanda H, Yoshikawa M, Tateya S, Nishino N, et al. The t-SNAREs syntaxin4 and SNAP23 but not v-SNARE VAMP2 are indispensable to tether GLUT4 vesicles at the plasma membrane in adipocyte. Biochem Biophys Res Commun. 2010;391:1336-41 pubmed publisher
  16. Katagiri H, Terasaki J, Murata T, Ishihara H, Ogihara T, Inukai K, et al. A novel isoform of syntaxin-binding protein homologous to yeast Sec1 expressed ubiquitously in mammalian cells. J Biol Chem. 1995;270:4963-6 pubmed
    ..bound to glutathione S-transferase-syntaxin 1A and, although with lower affinity, to glutathione S-transferase-syntaxin 4 fusion protein...
  17. Oh E, Thurmond D. Munc18c depletion selectively impairs the sustained phase of insulin release. Diabetes. 2009;58:1165-74 pubmed publisher
    The Sec1/Munc18 protein Munc18c has been implicated in Syntaxin 4-mediated exocytosis events, although its purpose in exocytosis has remained elusive...
  18. Fukuda N, Emoto M, Nakamori Y, Taguchi A, Miyamoto S, Uraki S, et al. DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes. Diabetes. 2009;58:377-84 pubmed publisher
    ..These findings indicate that DOC2b is a positive SNARE regulator for GLUT4 vesicle fusion and mediates insulin-stimulated glucose transport in adipocytes. ..
  19. Kennedy M, Davison I, Robinson C, Ehlers M. Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines. Cell. 2010;141:524-35 pubmed publisher
    ..Exocytosis occurs at microdomains enriched in the plasma membrane t-SNARE syntaxin 4 (Stx4), and disruption of Stx4 impairs both spine exocytosis and long-term potentiation (LTP) at hippocampal ..
  20. Wiseman D, Kalwat M, Thurmond D. Stimulus-induced S-nitrosylation of Syntaxin 4 impacts insulin granule exocytosis. J Biol Chem. 2011;286:16344-54 pubmed publisher
    ..stress serving as a mechanistic basis for insulin secretory dysfunction, we identified the t-SNARE protein Syntaxin 4 as a target of modification by S-nitrosylation...
  21. Pagan J, Wylie F, Joseph S, Widberg C, Bryant N, James D, et al. The t-SNARE syntaxin 4 is regulated during macrophage activation to function in membrane traffic and cytokine secretion. Curr Biol. 2003;13:156-60 pubmed
    ..A subset of t-SNAREs (Syntaxin 4/SNAP23/Munc18c) known to control regulated exocytosis in other cell types was substantially increased by LPS in ..
  22. Macaulay S, Grusovin J, Stoichevska V, Ryan J, Castelli L, Ward C. Cellular munc18c levels can modulate glucose transport rate and GLUT4 translocation in 3T3L1 cells. FEBS Lett. 2002;528:154-60 pubmed
    Munc18c has been shown to bind syntaxin 4 and to play a role in GLUT4 translocation and glucose transport, although this role is as yet poorly defined...
  23. Jewell J, Luo W, Oh E, Wang Z, Thurmond D. Filamentous actin regulates insulin exocytosis through direct interaction with Syntaxin 4. J Biol Chem. 2008;283:10716-26 pubmed publisher
    ..Toward this end we show here that both Syntaxin 1A and Syntaxin 4 associated with F-actin in MIN6 cells and that each interaction was rapidly and transiently diminished by ..
  24. Nechiporuk T, Fernandez T, Vasioukhin V. Failure of epithelial tube maintenance causes hydrocephalus and renal cysts in Dlg5-/- mice. Dev Cell. 2007;13:338-50 pubmed
    ..Dlg5 travels with cadherin-containing vesicles and binds to syntaxin 4, a t-SNARE protein that regulates fusion of transport vesicles with the lateral membrane domain...
  25. Veale K, Offenhäuser C, Lei N, Stanley A, Stow J, Murray R. VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration. Exp Cell Res. 2011;317:1817-29 pubmed publisher
    ..By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and ..
  26. Buxton P, Zhang X, Walsh B, Sriratana A, Schenberg I, Manickam E, et al. Identification and characterization of Snapin as a ubiquitously expressed SNARE-binding protein that interacts with SNAP23 in non-neuronal cells. Biochem J. 2003;375:433-40 pubmed
    ..Finally, we show that Snapin is able to form a ternary complex with SNAP23 and syntaxin 4, suggesting that it is a component of non-neuronal SNARE complexes...
  27. Thurmond D, Oh E, Miller R. Potential Site Effects and Transgene Expression Discrepancies in Mouse Lifespan Studies. Cell Metab. 2015;22:346-7 pubmed publisher
  28. Pooley R, Moynihan K, Soukoulis V, Reddy S, Francis R, Lo C, et al. Murine CENPF interacts with syntaxin 4 in the regulation of vesicular transport. J Cell Sci. 2008;121:3413-21 pubmed publisher
    b>Syntaxin 4 is a component of the SNARE complex that regulates membrane docking and fusion...
  29. Gerst J. SNAREs and SNARE regulators in membrane fusion and exocytosis. Cell Mol Life Sci. 1999;55:707-34 pubmed
    ..g. 'SNARE-masters') in mediating events leading to membrane fusion. A model to illustrate the dynamic cycling of SNAREs between fusion-incompetent and fusion-competent states, called the SNARE cycle, is presented. ..
  30. Wyman A, Chi M, Riley J, Carayannopoulos M, Yang C, Coker K, et al. Syntaxin 4 expression affects glucose transporter 8 translocation and embryo survival. Mol Endocrinol. 2003;17:2096-102 pubmed
    ..b>Syntaxin 4 is the t-SNARE critical for insulin-stimulated glucose transporter 4 (GLUT4)-plasma membrane fusion in ..
  31. Hasan N, Corbin D, Hu C. Fusogenic pairings of vesicle-associated membrane proteins (VAMPs) and plasma membrane t-SNAREs--VAMP5 as the exception. PLoS ONE. 2010;5:e14238 pubmed publisher
    ..These data indicate that VAMPs have differential membrane fusion capacities, and imply that with the exception of VAMP5, VAMPs are essentially redundant in mediating fusion with plasma membrane t-SNAREs. ..
  32. Min J, Okada S, Kanzaki M, Elmendorf J, Coker K, Ceresa B, et al. Synip: a novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes. Mol Cell. 1999;3:751-60 pubmed
    ..transport and GLUT4 translocation require regulated interactions between the v-SNARE, VAMP2, and the t-SNARE, syntaxin 4. We have isolated a novel syntaxin 4-binding protein, Synip, which specifically interacts with syntaxin 4...
  33. Lehtonen S, Riento K, Olkkonen V, Lehtonen E. Syntaxin 3 and Munc-18-2 in epithelial cells during kidney development. Kidney Int. 1999;56:815-26 pubmed
    ..The results show that Munc-18-2 and syntaxin 3 form a complex in vivo and suggest that they participate in epithelial cell differentiation and targeted vesicle transport processes in the developing kidney. ..
  34. Cosen Binker L, Binker M, Wang C, Hong W, Gaisano H. VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis. J Clin Invest. 2008;118:2535-51 pubmed publisher
    ..These findings indicate that VAMP8 is the ZG-SNARE that mediates basolateral exocytosis in alcoholic pancreatitis and that VAMP8 is critical for ZG-ZG homotypic fusion. ..
  35. Kioumourtzoglou D, Gould G, Bryant N. Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism. Mol Cell Biol. 2014;34:1271-9 pubmed publisher
    ..Hence, this report provides molecular detail of how the cell alters membrane traffic in response to an external stimulus, in this case, insulin...
  36. Umahara M, Okada S, Yamada E, Saito T, Ohshima K, Hashimoto K, et al. Tyrosine phosphorylation of Munc18c regulates platelet-derived growth factor-stimulated glucose transporter 4 translocation in 3T3L1 adipocytes. Endocrinology. 2008;149:40-9 pubmed
    ..To address the mechanism of PDGF action, we have determined that the Syntaxin 4 negative regulatory protein, Munc18c, undergoes PDGF-stimulated phosphorylation on tyrosine residue 521...
  37. Oh E, Miller R, Thurmond D. Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan. Cell Metab. 2015;22:499-507 pubmed publisher
    ..Peripheral responses to insulin can be augmented by overexpression of Syntaxin 4 (Syn4), a plasma-membrane-localized SNARE protein...
  38. Shirai K, Hagiwara N, Horigome T, Hirose Y, Kadono N, Hirai Y. Extracellularly Extruded Syntaxin-4 Binds to Laminin and Syndecan-1 to Regulate Mammary Epithelial Morphogenesis. J Cell Biochem. 2017;118:686-698 pubmed publisher
    ..Thus, temporal extracellular extrusion of syntaxin-4 emerged as a novel regulatory element for laminin-induced mammary epithelial cell behaviors. J. Cell. Biochem. 118: 686-698, 2017. © 2016 Wiley Periodicals, Inc. ..
  39. Hagiwara N, Kadono N, Miyazaki T, Maekubo K, Hirai Y. Extracellular syntaxin4 triggers the differentiation program in teratocarcinoma F9 cells that impacts cell adhesion properties. Cell Tissue Res. 2013;354:581-91 pubmed publisher
    ..These results demonstrate the involvement of a non-directional stimulation of extracellular syntaxin4 in the functional and morphological differentiation of F9 cells. ..
  40. Kepner E, Yoder S, Oh E, Kalwat M, Wang Z, Quilliam L, et al. Cool-1/?PIX functions as a guanine nucleotide exchange factor in the cycling of Cdc42 to regulate insulin secretion. Am J Physiol Endocrinol Metab. 2011;301:E1072-80 pubmed publisher
  41. Suzuki K, Verma I. Phosphorylation of SNAP-23 by IkappaB kinase 2 regulates mast cell degranulation. Cell. 2008;134:485-95 pubmed publisher
    ..The findings suggest that IKK2 is a central player in allergic reactions. ..