Weimer Robby M, Richmond Janet E, Davis Warren S, Hadwiger Gayla, Nonet Michael L, Jorgensen Erik M
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA.
Nat Neurosci. 2003 Oct;6(10):1023-30. doi: 10.1038/nn1118. Epub 2003 Sep 14.
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.
Sec1相关蛋白在真核细胞中大多数（即便不是全部）膜运输途径中发挥作用。神经元中突触小泡胞吐作用所需的Sec1相关蛋白是UNC-18。目前正在考虑几种关于UNC-18在小泡胞吐作用过程中功能的模型。我们通过对线虫秀丽隐杆线虫的unc-18突变体进行表征来测试这些模型。在没有UNC-18的情况下，易于释放的池的大小会严重减小。我们的结果表明，几乎不存在具有融合能力的小泡并非由 syntaxin水平降低、syntaxin定位错误、融合缺陷或引发过程中未能打开syntaxin所致。相反，我们发现在unc-18突变体中，活性区对接小泡减少，这表明UNC-18直接或间接地作为小泡对接的促进因子发挥作用。
