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PMID: 10526333 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

UNC-13 is required for synaptic vesicle fusion in C. elegans.

Nature neuroscience ·Vol. 2 ·No. 11 ·1999-11-00 ·Pages 959-64

Richmond JE, Davis WS, Jorgensen EM

Abstract

We analyzed the synaptic physiology of unc-13 mutants in the nematode C. elegans. Mutants of unc-13 had normal nervous system architecture, and the densities of synapses and postsynaptic receptors were normal at the neuromuscular junction. However, the number of synaptic vesicles at neuromuscular junctions was two- to threefold greater in unc-13 mutants than in wild-type animals. Most importantly, evoked release at both GABAergic and cholinergic synapses was almost absent in unc-13 null alleles, as determined by whole-cell, voltage-clamp techniques. Although mutant synapses had morphologically docked vesicles, these vesicles were not competent for release as assayed by spontaneous release in calcium-free solution or by the application of hyperosmotic saline. These experiments support models in which UNC-13 mediates either fusion of vesicles during exocytosis or priming of vesicles for fusion.

MeSH Terms
Alleles Animals Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins Carrier Proteins Helminth Proteins/genetics,physiology Mutation Nerve Tissue Proteins/genetics,physiology Neuromuscular Junction/physiology Synaptic Transmission/physiology Synaptic Vesicles/physiology
Chemicals
Caenorhabditis elegans Proteins Carrier Proteins Helminth Proteins Nerve Tissue Proteins phorbol ester binding protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Richmond J E
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA.
Davis W S
Jorgensen E M
References (32)
32 references, click to expand
  1. Serotonin inhibition of synaptic transmission: Galpha(0) decreases the abundance of UNC-13 at release sites.
    Neuron. 1999 Sep;24(1):231-42 PMID: 10677040
  2. The genetics of Caenorhabditis elegans.
    Genetics. 1974 May;77(1):71-94 PMID: 4366476
  3. Genetic organization of the region around UNC-15 (I), a gene affecting paramyosin in Caenorhabditis elegans.
    Genetics. 1980 Nov;96(3):639-48 PMID: 7262541
  4. Effects of hypertonic solutions on quantal transmitter release at the crayfish neuromuscular junction.
    J Physiol. 1982 Aug;329:185-202 PMID: 6128408
  5. A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5729-33 PMID: 2062851
  6. The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor.
    Biochem J. 1992 Nov 1;287 ( Pt 3):995-9 PMID: 1445255
  7. 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):409-18 PMID: 8221884
  8. Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin.
    Nature. 1993 Nov 25;366(6453):347-51 PMID: 8247129
  9. Specificity and regulation of a synaptic vesicle docking complex.
    Neuron. 1994 Aug;13(2):353-61 PMID: 8060616
  10. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo.
    Neuron. 1994 Nov;13(5):1099-108 PMID: 7946348
  11. Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.
    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):846-9 PMID: 7846064
  12. Characterization of the cysteine-rich region of the Caenorhabditis elegans protein Unc-13 as a high affinity phorbol ester receptor. Analysis of ligand-binding interactions, lipid cofactor requirements, and inhibitor sensitivity.
    J Biol Chem. 1995 May 5;270(18):10777-83 PMID: 7537738
  13. Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.
    J Biol Chem. 1995 Oct 20;270(42):25273-80 PMID: 7559667
  14. Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans.
    Nature. 1995 Nov 9;378(6553):196-9 PMID: 7477324
  15. Caenorhabditis elegans mutants resistant to inhibitors of acetylcholinesterase.
    Genetics. 1995 Jun;140(2):527-35 PMID: 7498734
  16. Definition of the readily releasable pool of vesicles at hippocampal synapses.
    Neuron. 1996 Jun;16(6):1197-207 PMID: 8663996
  17. Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin.
    J Biol Chem. 1997 Jan 24;272(4):2520-6 PMID: 8999968
  18. Regulation of protein kinase C.
    Curr Opin Cell Biol. 1997 Apr;9(2):161-7 PMID: 9069266
  19. Identification and characterization of the vesicular GABA transporter.
    Nature. 1997 Oct 23;389(6653):870-6 PMID: 9349821
  20. Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin.
    J Biol Chem. 1998 Jan 23;273(4):2192-8 PMID: 9442061
  21. C2-domains, structure and function of a universal Ca2+-binding domain.
    J Biol Chem. 1998 Jun 26;273(26):15879-82 PMID: 9632630
  22. Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release.
    Neuron. 1998 Jul;21(1):123-36 PMID: 9697857
  23. Retinal targets for calmodulin include proteins implicated in synaptic transmission.
    J Biol Chem. 1998 Nov 20;273(47):31297-307 PMID: 9813038
  24. The Caenorhabditis elegans gene unc-25 encodes glutamic acid decarboxylase and is required for synaptic transmission but not synaptic development.
    J Neurosci. 1999 Jan 15;19(2):539-48 PMID: 9880574
  25. Differential expression of two novel Munc13 proteins in rat brain.
    Biochem J. 1999 Feb 1;337 ( Pt 3):363-71 PMID: 9895278
  26. Genetic evidence for an equilibrium between docked and undocked vesicles.
    Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):299-306 PMID: 10212478
  27. Regulation of the UNC-18-Caenorhabditis elegans syntaxin complex by UNC-13.
    J Neurosci. 1999 Jun 15;19(12):4772-7 PMID: 10366611
  28. 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
  29. Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo.
    Neuron. 1999 Jul;23(3):593-605 PMID: 10433270
  30. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles.
    Nature. 1999 Jul 29;400(6743):457-61 PMID: 10440375
  31. One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction.
    Nat Neurosci. 1999 Sep;2(9):791-7 PMID: 10461217
  32. Drosophila UNC-13 is essential for synaptic transmission.
    Nat Neurosci. 1999 Nov;2(11):965-71 PMID: 10526334
Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1097-6256
Published
1999-11-00
Pages
959-64
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2585767
Subset
IM
Grants
NINDS NIH HHS · R01 NS034307 · United States
NINDS NIH HHS · R01 NS34307 · United States
NIMH NIH HHS · R03 MH059820-01 · United States
NIMH NIH HHS · R03 MHS9820-01 · United States
NIMH NIH HHS · R03 MH059820-02 · United States
AHRQ HHS · R03 HS009820 · United States
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