Defects in synaptic vesicle docking in unc-18 mutants

Robby M. Weimer; Janet E. Richmond; Warren S. Davis; Gayla Hadwiger; Michael L. Nonet; Erik M. Jorgensen

doi:10.1038/nn1118

Defects in synaptic vesicle docking in unc-18 mutants

Robby M. Weimer, Janet E. Richmond, Warren S. Davis, Gayla Hadwiger, Michael L. Nonet, Erik M. Jorgensen

Research output: Contribution to journal › Article › peer-review

214 Scopus citations

Abstract

Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.

Original language	English
Pages (from-to)	1023-1030
Number of pages	8
Journal	Nature neuroscience
Volume	6
Issue number	10
DOIs	https://doi.org/10.1038/nn1118
State	Published - Oct 1 2003

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title = "Defects in synaptic vesicle docking in unc-18 mutants",

abstract = "Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.",

author = "Weimer, {Robby M.} and Richmond, {Janet E.} and Davis, {Warren S.} and Gayla Hadwiger and Nonet, {Michael L.} and Jorgensen, {Erik M.}",

note = "Funding Information: We thank J. Rand for providing unc-18(md299) and antisera to UNC-18, M. Bastiani for providing the confocal microscope, the Caenorhabditis Genetics Center for providing unc-18(e234) and unc-18(e81),E.Maryon for providing the Pt09a9.10:gfp reporter construct, and J.-L. Bessereau, P. Rostaing and A. Triller for assistance with developing immuno-electron microscopy techniques. This work was supported by National Institutes of Health grants to J.E.R. and E.M.J., a US Public Health Service grant to M.L.N., and an INSERM Poste Vert grant to R.M.W.",

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AU - Weimer, Robby M.

AU - Richmond, Janet E.

AU - Davis, Warren S.

AU - Hadwiger, Gayla

AU - Nonet, Michael L.

AU - Jorgensen, Erik M.

N1 - Funding Information: We thank J. Rand for providing unc-18(md299) and antisera to UNC-18, M. Bastiani for providing the confocal microscope, the Caenorhabditis Genetics Center for providing unc-18(e234) and unc-18(e81),E.Maryon for providing the Pt09a9.10:gfp reporter construct, and J.-L. Bessereau, P. Rostaing and A. Triller for assistance with developing immuno-electron microscopy techniques. This work was supported by National Institutes of Health grants to J.E.R. and E.M.J., a US Public Health Service grant to M.L.N., and an INSERM Poste Vert grant to R.M.W.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.

AB - Sec1-related proteins function in most, if not all, membrane trafficking pathways in eukaryotic cells. The Sec1-related protein required in neurons for synaptic vesicle exocytosis is UNC-18. Several models for UNC-18 function during vesicle exocytosis are under consideration. We have tested these models by characterizing unc-18 mutants of the nematode Caenorhabditis elegans. In the absence of UNC-18, the size of the readily releasable pool is severely reduced. Our results show that the near absence of fusion-competent vesicles is not caused by a reduction in syntaxin levels, by a mislocalization of syntaxin, by a defect in fusion or by a failure to open syntaxin during priming. Rather, we found a reduction of docked vesicles at the active zone in unc-18 mutants, suggesting that UNC-18 functions, directly or indirectly, as a facilitator of vesicle docking.

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Defects in synaptic vesicle docking in unc-18 mutants

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