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PMID: 17645391 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Open syntaxin docks synaptic vesicles.

PLoS biology ·Vol. 5 ·No. 8 ·2007-08-00 ·Pages e198

Hammarlund M, Palfreyman MT, Watanabe S, Olsen S, Jorgensen EM

Abstract

Synaptic vesicles dock to the plasma membrane at synapses to facilitate rapid exocytosis. Docking was originally proposed to require the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) proteins; however, perturbation studies suggested that docking was independent of the SNARE proteins. We now find that the SNARE protein syntaxin is required for docking of all vesicles at synapses in the nematode Caenorhabditis elegans. The active zone protein UNC-13, which interacts with syntaxin, is also required for docking in the active zone. The docking defects in unc-13 mutants can be fully rescued by overexpressing a constitutively open form of syntaxin, but not by wild-type syntaxin. These experiments support a model for docking in which UNC-13 converts syntaxin from the closed to the open state, and open syntaxin acts directly in docking vesicles to the plasma membrane. These data provide a molecular basis for synaptic vesicle docking.

MeSH Terms
Animals Caenorhabditis elegans/cytology,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Carrier Proteins Cell Membrane/metabolism,ultrastructure Cell Shape Exocytosis/physiology Membrane Fusion/physiology Mosaicism Neuromuscular Junction/physiology,ultrastructure Neuromuscular Nondepolarizing Agents/pharmacology Neurons/cytology,physiology Patch-Clamp Techniques Qa-SNARE Proteins/genetics,metabolism,ultrastructure Recombinant Fusion Proteins/genetics,metabolism Synapses/drug effects,metabolism,ultrastructure Synaptic Vesicles/metabolism,ultrastructure Tubocurarine/pharmacology gamma-Aminobutyric Acid/metabolism
Chemicals
Caenorhabditis elegans Proteins Carrier Proteins Neuromuscular Nondepolarizing Agents Qa-SNARE Proteins Recombinant Fusion Proteins phorbol ester binding protein gamma-Aminobutyric Acid Tubocurarine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hammarlund Marc
Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
Palfreyman Mark T
Watanabe Shigeki
Olsen Shawn
Jorgensen Erik M
References (93)
93 references, click to expand
  1. SynCAM, a synaptic adhesion molecule that drives synapse assembly.
    Science. 2002 Aug 30;297(5586):1525-31 PMID: 12202822
  2. Geranylgeranylated SNAREs are dominant inhibitors of membrane fusion.
    J Cell Biol. 2000 Oct 16;151(2):453-66 PMID: 11038190
  3. Depolarization redistributes synaptic membrane and creates a gradient of vesicles on the synaptic body at a ribbon synapse.
    Neuron. 2002 Nov 14;36(4):649-59 PMID: 12441054
  4. Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion.
    J Neurosci. 2006 Jun 21;26(25):6668-76 PMID: 16793874
  5. Drosophila syntaxin is required for cell viability and may function in membrane formation and stabilization.
    Genetics. 1996 Dec;144(4):1713-24 PMID: 8978057
  6. Membrane fusion induced by neuronal SNAREs transits through hemifusion.
    J Biol Chem. 2005 Aug 26;280(34):30538-41 PMID: 15980065
  7. EXP-1 is an excitatory GABA-gated cation channel.
    Nat Neurosci. 2003 Nov;6(11):1145-52 PMID: 14555952
  8. Membrane fusion.
    Cell. 2003 Feb 21;112(4):519-33 PMID: 12600315
  9. Analysis of knock-out mice to determine the role of HPC-1/syntaxin 1A in expressing synaptic plasticity.
    J Neurosci. 2006 May 24;26(21):5767-76 PMID: 16723534
  10. A post-docking role for synaptobrevin in synaptic vesicle fusion.
    Neuron. 1994 Jun;12(6):1269-79 PMID: 8011337
  11. A Drosophila SNAP-25 null mutant reveals context-dependent redundancy with SNAP-24 in neurotransmission.
    Genetics. 2002 Sep;162(1):259-71 PMID: 12242238
  12. SNARE complex formation is triggered by Ca2+ and drives membrane fusion.
    Cell. 1999 Apr 16;97(2):165-74 PMID: 10219238
  13. Stable SNARE complex prior to evoked synaptic vesicle fusion revealed by fluorescence resonance energy transfer.
    J Biol Chem. 2001 Jan 19;276(3):1766-71 PMID: 11035043
  14. The architecture of the active zone in the presynaptic nerve terminal.
    Physiology (Bethesda). 2004 Oct;19:262-70 PMID: 15381754
  15. DNA transformation.
    Methods Cell Biol. 1995;48:451-82 PMID: 8531738
  16. Response: meaningless minis?
    Trends Neurosci. 2002 Aug;25(8):386-7 PMID: 12127747
  17. Clathrin-mediated endocytosis near active zones in snake motor boutons.
    J Neurosci. 2000 Nov 1;20(21):7986-93 PMID: 11050119
  18. UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains.
    J Neurosci. 2006 Aug 2;26(31):8040-7 PMID: 16885217
  19. Endocytic active zones: hot spots for endocytosis in vertebrate neuromuscular terminals.
    J Neurosci. 1999 Jun 15;19(12):4855-66 PMID: 10366620
  20. Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction.
    J Cell Biol. 1973 May;57(2):499-524 PMID: 4348791
  21. The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor.
    J Neurosci. 1999 Jul 1;19(13):5348-59 PMID: 10377345
  22. Antagonistic regulation of synaptic vesicle priming by Tomosyn and UNC-13.
    Neuron. 2006 Aug 3;51(3):303-15 PMID: 16880125
  23. Vesicle tethering complexes in membrane traffic.
    J Cell Sci. 2002 Jul 1;115(Pt 13):2627-37 PMID: 12077354
  24. Roles of SNARE proteins and synaptotagmin I in synaptic transmission: studies at the Drosophila neuromuscular synapse.
    Neurosignals. 2003 Jan-Feb;12(1):13-30 PMID: 12624525
  25. Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila.
    Neuron. 1995 Sep;15(3):663-73 PMID: 7546745
  26. Parathyroid ultrastructure after aldehyde fixation, high-pressure freezing, or microwave irradiation.
    J Histochem Cytochem. 1987 Dec;35(12):1415-24 PMID: 3680934
  27. Members of the synaptobrevin/vesicle-associated membrane protein (VAMP) family in Drosophila are functionally interchangeable in vivo for neurotransmitter release and cell viability.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13867-72 PMID: 12364587
  28. Three-dimensional organization of cell adhesion junctions at synapses and dendritic spines in area CA1 of the rat hippocampus.
    J Comp Neurol. 1998 Mar 30;393(1):58-68 PMID: 9520101
  29. Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs.
    Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12571-6 PMID: 10535963
  30. Spontaneous subthreshold activity at motor nerve endings.
    J Physiol. 1952 May;117(1):109-28 PMID: 14946732
  31. A conformational switch in syntaxin during exocytosis: role of munc18.
    EMBO J. 1999 Aug 16;18(16):4372-82 PMID: 10449403
  32. The synaptic protein syntaxin1 is required for cellularization of Drosophila embryos.
    J Cell Biol. 1997 Aug 25;138(4):861-75 PMID: 9265652
  33. Developmental regulation of glutamate receptor field size by nonvesicular glutamate release.
    Nat Neurosci. 2002 Feb;5(2):141-6 PMID: 11753421
  34. Preservation of C. elegans tissue via high-pressure freezing and freeze-substitution for ultrastructural analysis and immunocytochemistry.
    Methods Mol Biol. 2006;351:203-21 PMID: 16988436
  35. Determinants of liposome fusion mediated by synaptic SNARE proteins.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2858-63 PMID: 14981239
  36. Multiple intermediates in SNARE-induced membrane fusion.
    Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19731-6 PMID: 17167056
  37. The Caenorhabditis elegans unc-64 locus encodes a syntaxin that interacts genetically with synaptobrevin.
    Mol Biol Cell. 1998 Jun;9(6):1235-52 PMID: 9614171
  38. The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering.
    Cell. 2006 Nov 17;127(4):817-30 PMID: 17110339
  39. Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis.
    Nature. 1993 Jan 28;361(6410):350-3 PMID: 8426654
  40. One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction.
    Nat Neurosci. 1999 Sep;2(9):791-7 PMID: 10461217
  41. The synaptic vesicle cycle: a cascade of protein-protein interactions.
    Nature. 1995 Jun 22;375(6533):645-53 PMID: 7791897
  42. Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12186-91 PMID: 9342384
  43. Use of aldehyde fixatives to determine the rate of synaptic transmitter release.
    J Exp Biol. 1980 Dec;89:19-29 PMID: 6110693
  44. Definition of the readily releasable pool of vesicles at hippocampal synapses.
    Neuron. 1996 Jun;16(6):1197-207 PMID: 8663996
  45. Functional analysis of conserved structural elements in yeast syntaxin Vam3p.
    J Biol Chem. 2001 Jul 27;276(30):28598-605 PMID: 11349128
  46. Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers.
    J Neurosci. 1996 Sep 1;16(17):5443-56 PMID: 8757257
  47. Dissecting docking and tethering of secretory vesicles at the target membrane.
    EMBO J. 2006 Aug 23;25(16):3725-37 PMID: 16902411
  48. Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction.
    J Cell Biol. 1973 May;57(2):315-44 PMID: 4348786
  49. Ectopic release of synaptic vesicles.
    Neuron. 2003 Dec 18;40(6):1173-83 PMID: 14687551
  50. Ultrastructural correlates of transmitter release in presynaptic areas of lamprey reticulospinal axons.
    J Neurosci. 1985 May;5(5):1188-201 PMID: 2860213
  51. The endocytic machinery in nerve terminals surrounds sites of exocytosis.
    Curr Biol. 1999 Dec 2;9(23):1411-4 PMID: 10607569
  52. Regulation of transmitter release by Unc-13 and its homologues.
    Curr Opin Neurobiol. 2000 Jun;10(3):303-11 PMID: 10851170
  53. Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin.
    J Biol Chem. 1998 Jan 23;273(4):2192-8 PMID: 9442061
  54. Block of transmitter release by botulinum C1 action on syntaxin at the squid giant synapse.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14871-6 PMID: 9405706
  55. Quantitative ultrastructural analysis of hippocampal excitatory synapses.
    J Neurosci. 1997 Aug 1;17(15):5858-67 PMID: 9221783
  56. The structure of the nervous system of the nematode Caenorhabditis elegans.
    Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340 PMID: 22462104
  57. Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors.
    J Cell Biol. 2000 Jul 10;150(1):105-17 PMID: 10893260
  58. Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23.
    Cell. 2003 Jul 11;114(1):75-86 PMID: 12859899
  59. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.
    Nature. 1998 Sep 24;395(6700):347-53 PMID: 9759724
  60. Structural changes after transmitter release at the frog neuromuscular junction.
    J Cell Biol. 1981 Mar;88(3):564-80 PMID: 6260814
  61. Preservation of immunoreactivity and fine structure of adult C. elegans tissues using high-pressure freezing.
    J Histochem Cytochem. 2004 Jan;52(1):1-12 PMID: 14688212
  62. Docking of secretory vesicles is syntaxin dependent.
    PLoS One. 2006 Dec 27;1:e126 PMID: 17205130
  63. Absence of junctional glutamate receptor clusters in Drosophila mutants lacking spontaneous transmitter release.
    Science. 2001 Jul 20;293(5529):514-7 PMID: 11463917
  64. Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.
    PLoS Biol. 2006 Jul;4(8):e261 PMID: 16895441
  65. Evidence for ectopic neurotransmission at a neuronal synapse.
    Science. 2005 Jul 15;309(5733):446-51 PMID: 16020730
  66. High-pressure freezing, cellular tomography, and structural cell biology.
    Biotechniques. 2006 Aug;41(2):137, 139, 141 passim PMID: 16925014
  67. UNC-13 interaction with syntaxin is required for synaptic transmission.
    Curr Biol. 2005 Dec 20;15(24):2236-42 PMID: 16271476
  68. Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins.
    J Cell Biol. 2002 Sep 2;158(5):929-40 PMID: 12213837
  69. An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming.
    Nature. 2001 Jul 19;412(6844):338-41 PMID: 11460165
  70. Unraveling the mechanisms of synaptotagmin and SNARE function in neurotransmitter release.
    Trends Cell Biol. 2006 Jul;16(7):339-50 PMID: 16698267
  71. SNAP receptors implicated in vesicle targeting and fusion.
    Nature. 1993 Mar 25;362(6418):318-24 PMID: 8455717
  72. SNAREpins: minimal machinery for membrane fusion.
    Cell. 1998 Mar 20;92(6):759-72 PMID: 9529252
  73. Contribution to the problem of structural organization of the presynaptic area.
    Brain Res. 1969 Jan;12(1):10-8 PMID: 4184686
  74. Synaptic vesicle docking: a putative role for the Munc18/Sec1 protein family.
    Curr Top Dev Biol. 2005;65:83-113 PMID: 15642380
  75. The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.
    J Cell Biol. 1996 Nov;135(3):767-79 PMID: 8909549
  76. Drosophila UNC-13 is essential for synaptic transmission.
    Nat Neurosci. 1999 Nov;2(11):965-71 PMID: 10526334
  77. Morphological correlates of functionally defined synaptic vesicle populations.
    Nat Neurosci. 2001 Apr;4(4):391-5 PMID: 11276229
  78. Activity-dependent changes in partial VAMP complexes during neurotransmitter release.
    Nat Neurosci. 1999 Dec;2(12):1078-83 PMID: 10570484
  79. Sequential SNARE assembly underlies priming and triggering of exocytosis.
    Neuron. 2001 Apr;30(1):161-70 PMID: 11343652
  80. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy.
    Cell. 1997 Aug 8;90(3):523-35 PMID: 9267032
  81. Variation in the number, location and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses.
    Neuropharmacology. 1995 Nov;34(11):1387-95 PMID: 8606788
  82. Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells.
    J Neurosci. 2001 Sep 1;21(17):6666-72 PMID: 11517256
  83. Genes required for GABA function in Caenorhabditis elegans.
    Nature. 1993 Jul 22;364(6435):334-7 PMID: 8332190
  84. [Synaptic vesicles and pouches at the level of "active zones" of the neuromuscular junction].
    C R Acad Hebd Seances Acad Sci D. 1970 Dec 21;271(25):2346-9 PMID: 4995202
  85. A model for central synaptic junctional complex formation based on the differential adhesive specificities of the cadherins.
    Neuron. 1996 Sep;17(3):423-34 PMID: 8816706
  86. SNARE-driven, 25-millisecond vesicle fusion in vitro.
    Biophys J. 2005 Oct;89(4):2458-72 PMID: 16055544
  87. Electron microscopy of presynaptic organelles of the spinal cord.
    J Anat. 1963 Jan;97:101-6 PMID: 13949972
  88. Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis.
    Cell. 1999 Dec 23;99(7):713-22 PMID: 10619425
  89. UNC-13 is required for synaptic vesicle fusion in C. elegans.
    Nat Neurosci. 1999 Nov;2(11):959-64 PMID: 10526333
  90. v-SNAREs control exocytosis of vesicles from priming to fusion.
    EMBO J. 2005 Jun 15;24(12):2114-26 PMID: 15920476
  91. The structure of the ventral nerve cord of Caenorhabditis elegans.
    Philos Trans R Soc Lond B Biol Sci. 1976 Aug 10;275(938):327-48 PMID: 8806
  92. SNARE-mediated lipid mixing depends on the physical state of the vesicles.
    Biophys J. 2006 Mar 15;90(6):2062-74 PMID: 16361343
  93. Munc13-1 C1 domain activation lowers the energy barrier for synaptic vesicle fusion.
    J Neurosci. 2007 Jan 31;27(5):1200-10 PMID: 17267576
Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
Published
2007-08-00
Pages
e198
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC1914072
Subset
IM
Grants
NINDS NIH HHS · R01 NS034307 · United States
NINDS NIH HHS · R37 NS034307 · United States
NINDS NIH HHS · NS034307 · United States
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