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. 1994 Feb 15;91(4):1445–1449. doi: 10.1073/pnas.91.4.1445

n-Sec1: a neural-specific syntaxin-binding protein.

J Pevsner 1, S C Hsu 1, R H Scheller 1
PMCID: PMC43176  PMID: 8108429

Abstract

We have identified n-Sec1, a rat brain homolog of the yeast Sec1p protein that participates in the constitutive secretory pathway between the Golgi apparatus and the plasma membrane. The rat brain cDNA is predicted to encode a 68-kDa protein with 65% amino acid identity to Drosophila rop, 59% identity to Caenorhabditis elegans unc-18, and 27% identity to Saccharomyces cerevisiae Sec1p. By RNA blot analysis, n-Sec1 mRNA expression is neural-specific. An anti-peptide antiserum directed against the n-Sec1 carboxyl terminus detects a 68-kDa protein in rat brain cytosol and membranes, but not in peripheral tissues. In the presence of syntaxin 1a, a plasma membrane protein implicated in synaptic vesicle docking, n-Sec1 becomes membrane-associated. n-Sec1 binds to syntaxin 1a, 2, and 3 fusion proteins coupled to agarose beads, but not to syntaxin 4 fusion protein or beads coupled to a variety of other proteins. These findings indicate that n-Sec1 is a neural-specific, syntaxin-binding protein that may participate in the regulation of synaptic vesicle docking and fusion.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aalto M. K., Keränen S., Ronne H. A family of proteins involved in intracellular transport. Cell. 1992 Jan 24;68(2):181–182. doi: 10.1016/0092-8674(92)90462-l. [DOI] [PubMed] [Google Scholar]
  2. Aalto M. K., Ronne H., Keränen S. Yeast syntaxins Sso1p and Sso2p belong to a family of related membrane proteins that function in vesicular transport. EMBO J. 1993 Nov;12(11):4095–4104. doi: 10.1002/j.1460-2075.1993.tb06093.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aalto M. K., Ruohonen L., Hosono K., Keränen S. Cloning and sequencing of the yeast Saccharomyces cerevisiae SEC1 gene localized on chromosome IV. Yeast. 1991 Aug-Sep;7(6):643–650. doi: 10.1002/yea.320070613. [DOI] [PubMed] [Google Scholar]
  4. Adams M. D., Dubnick M., Kerlavage A. R., Moreno R., Kelley J. M., Utterback T. R., Nagle J. W., Fields C., Venter J. C. Sequence identification of 2,375 human brain genes. Nature. 1992 Feb 13;355(6361):632–634. doi: 10.1038/355632a0. [DOI] [PubMed] [Google Scholar]
  5. Bennett M. K., Calakos N., Scheller R. H. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 1992 Jul 10;257(5067):255–259. doi: 10.1126/science.1321498. [DOI] [PubMed] [Google Scholar]
  6. Bennett M. K., García-Arrarás J. E., Elferink L. A., Peterson K., Fleming A. M., Hazuka C. D., Scheller R. H. The syntaxin family of vesicular transport receptors. Cell. 1993 Sep 10;74(5):863–873. doi: 10.1016/0092-8674(93)90466-4. [DOI] [PubMed] [Google Scholar]
  7. Bennett M. K., Scheller R. H. The molecular machinery for secretion is conserved from yeast to neurons. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2559–2563. doi: 10.1073/pnas.90.7.2559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bowser R., Müller H., Govindan B., Novick P. Sec8p and Sec15p are components of a plasma membrane-associated 19.5S particle that may function downstream of Sec4p to control exocytosis. J Cell Biol. 1992 Sep;118(5):1041–1056. doi: 10.1083/jcb.118.5.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cain C. C., Trimble W. S., Lienhard G. E. Members of the VAMP family of synaptic vesicle proteins are components of glucose transporter-containing vesicles from rat adipocytes. J Biol Chem. 1992 Jun 15;267(17):11681–11684. [PubMed] [Google Scholar]
  10. Clary D. O., Griff I. C., Rothman J. E. SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast. Cell. 1990 May 18;61(4):709–721. doi: 10.1016/0092-8674(90)90482-t. [DOI] [PubMed] [Google Scholar]
  11. Dascher C., Ossig R., Gallwitz D., Schmitt H. D. Identification and structure of four yeast genes (SLY) that are able to suppress the functional loss of YPT1, a member of the RAS superfamily. Mol Cell Biol. 1991 Feb;11(2):872–885. doi: 10.1128/mcb.11.2.872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. De Camilli P. Exocytosis goes with a SNAP. Nature. 1993 Jul 29;364(6436):387–388. doi: 10.1038/364387a0. [DOI] [PubMed] [Google Scholar]
  13. Fischer von Mollard G., Mignery G. A., Baumert M., Perin M. S., Hanson T. J., Burger P. M., Jahn R., Südhof T. C. rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1988–1992. doi: 10.1073/pnas.87.5.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gerst J. E., Rodgers L., Riggs M., Wigler M. SNC1, a yeast homolog of the synaptic vesicle-associated membrane protein/synaptobrevin gene family: genetic interactions with the RAS and CAP genes. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4338–4342. doi: 10.1073/pnas.89.10.4338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Griff I. C., Schekman R., Rothman J. E., Kaiser C. A. The yeast SEC17 gene product is functionally equivalent to mammalian alpha-SNAP protein. J Biol Chem. 1992 Jun 15;267(17):12106–12115. [PubMed] [Google Scholar]
  16. Hess D. T., Slater T. M., Wilson M. C., Skene J. H. The 25 kDa synaptosomal-associated protein SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS. J Neurosci. 1992 Dec;12(12):4634–4641. doi: 10.1523/JNEUROSCI.12-12-04634.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hosono R., Hekimi S., Kamiya Y., Sassa T., Murakami S., Nishiwaki K., Miwa J., Taketo A., Kodaira K. I. The unc-18 gene encodes a novel protein affecting the kinetics of acetylcholine metabolism in the nematode Caenorhabditis elegans. J Neurochem. 1992 Apr;58(4):1517–1525. doi: 10.1111/j.1471-4159.1992.tb11373.x. [DOI] [PubMed] [Google Scholar]
  18. Kelly R. B. The cell biology of the nerve terminal. Neuron. 1988 Aug;1(6):431–438. doi: 10.1016/0896-6273(88)90174-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Malhotra V., Orci L., Glick B. S., Block M. R., Rothman J. E. Role of an N-ethylmaleimide-sensitive transport component in promoting fusion of transport vesicles with cisternae of the Golgi stack. Cell. 1988 Jul 15;54(2):221–227. doi: 10.1016/0092-8674(88)90554-5. [DOI] [PubMed] [Google Scholar]
  20. Matteoli M., Takei K., Cameron R., Hurlbut P., Johnston P. A., Südhof T. C., Jahn R., De Camilli P. Association of Rab3A with synaptic vesicles at late stages of the secretory pathway. J Cell Biol. 1991 Nov;115(3):625–633. doi: 10.1083/jcb.115.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Novick P., Brennwald P., Walworth N. C., Kabcenell A. K., Garrett M., Moya M., Roberts D., Müller H., Govindan B., Bowser R. The cycle of SEC4 function in vesicular transport. Ciba Found Symp. 1993;176:218–232. [PubMed] [Google Scholar]
  22. Novick P., Field C., Schekman R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell. 1980 Aug;21(1):205–215. doi: 10.1016/0092-8674(80)90128-2. [DOI] [PubMed] [Google Scholar]
  23. Protopopov V., Govindan B., Novick P., Gerst J. E. Homologs of the synaptobrevin/VAMP family of synaptic vesicle proteins function on the late secretory pathway in S. cerevisiae. Cell. 1993 Sep 10;74(5):855–861. doi: 10.1016/0092-8674(93)90465-3. [DOI] [PubMed] [Google Scholar]
  24. Pryer N. K., Wuestehube L. J., Schekman R. Vesicle-mediated protein sorting. Annu Rev Biochem. 1992;61:471–516. doi: 10.1146/annurev.bi.61.070192.002351. [DOI] [PubMed] [Google Scholar]
  25. Rothman J. E., Orci L. Molecular dissection of the secretory pathway. Nature. 1992 Jan 30;355(6359):409–415. doi: 10.1038/355409a0. [DOI] [PubMed] [Google Scholar]
  26. Salminen A., Novick P. J. A ras-like protein is required for a post-Golgi event in yeast secretion. Cell. 1987 May 22;49(4):527–538. doi: 10.1016/0092-8674(87)90455-7. [DOI] [PubMed] [Google Scholar]
  27. Salzberg A., Cohen N., Halachmi N., Kimchie Z., Lev Z. The Drosophila Ras2 and Rop gene pair: a dual homology with a yeast Ras-like gene and a suppressor of its loss-of-function phenotype. Development. 1993 Apr;117(4):1309–1319. doi: 10.1242/dev.117.4.1309. [DOI] [PubMed] [Google Scholar]
  28. Söllner T., Bennett M. K., Whiteheart S. W., Scheller R. H., Rothman J. E. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell. 1993 Nov 5;75(3):409–418. doi: 10.1016/0092-8674(93)90376-2. [DOI] [PubMed] [Google Scholar]
  29. Söllner T., Whiteheart S. W., Brunner M., Erdjument-Bromage H., Geromanos S., Tempst P., Rothman J. E. SNAP receptors implicated in vesicle targeting and fusion. Nature. 1993 Mar 25;362(6418):318–324. doi: 10.1038/362318a0. [DOI] [PubMed] [Google Scholar]
  30. Südhof T. C., Jahn R. Proteins of synaptic vesicles involved in exocytosis and membrane recycling. Neuron. 1991 May;6(5):665–677. doi: 10.1016/0896-6273(91)90165-v. [DOI] [PubMed] [Google Scholar]
  31. Trimble W. S., Gray T. S., Elferink L. A., Wilson M. C., Scheller R. H. Distinct patterns of expression of two VAMP genes within the rat brain. J Neurosci. 1990 Apr;10(4):1380–1387. doi: 10.1523/JNEUROSCI.10-04-01380.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Whiteheart S. W., Brunner M., Wilson D. W., Wiedmann M., Rothman J. E. Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) bind to a multi-SNAP receptor complex in Golgi membranes. J Biol Chem. 1992 Jun 15;267(17):12239–12243. [PubMed] [Google Scholar]
  33. Wilson D. W., Wilcox C. A., Flynn G. C., Chen E., Kuang W. J., Henzel W. J., Block M. R., Ullrich A., Rothman J. E. A fusion protein required for vesicle-mediated transport in both mammalian cells and yeast. Nature. 1989 Jun 1;339(6223):355–359. doi: 10.1038/339355a0. [DOI] [PubMed] [Google Scholar]

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