Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.
Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.
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DOI：
10.1371/journal.pbio.0040261
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发表时间：
2006-07
期刊：
影响因子：
9.8
通讯作者：
Richmond, Janet E
中科院分区：
文献类型：
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作者：
Gracheva, Elena O;Burdina, Anna O;Holgado, Andrea M;Berthelot-Grosjean, Martine;Ackley, Brian D;Hadwiger, Gayla;Nonet, Michael L;Weimer, Robby M;Richmond, Janet E
秀丽隐杆线虫TOM-1与脊椎动物tomosyn（一种涉及组成性和调节性胞吐的调节的细胞溶质突触融合蛋白结合蛋白）是同源的。为了研究TOM-1在体内如何调节突触囊泡的胞吐作用，我们分析了C。线虫tom-1突变体。我们的电生理分析表明，诱发突触后反应在tom-1突变突触延长导致总电荷转移的两倍增加。在tom-1突变体中增强的反应与突触后反应动力学、神经元生长或突触发生的任何可检测的变化无关。然而，在超微结构水平上，我们观察到同时增加的质膜接触囊泡在汤姆-1突变突触，神经元表达的TOM-1逆转的表型。引发缺陷unc-13突变体显示质膜接触囊泡的急剧减少，表明这些囊泡主要代表了C.神经肌肉接头与此结论一致，tom-1突变体的高渗反应增强，表明引发的囊泡池增强。此外，unc-13突变体的突触缺陷在tom-1 unc-13双突变体中被部分抑制。这些数据表明，在完整的神经系统中，TOM-1负调节突触囊泡启动。 本文研究了突触融合蛋白结合蛋白tomosyn在突触传递中的作用。神经肌肉接头Tomosyn通过调节容易释放的囊泡池的大小来抑制囊泡引发。
Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses are prolonged leading to a two-fold increase in total charge transfer. The enhanced response in tom-1 mutants is not associated with any detectable changes in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis. However, at the ultrastructural level, we observe a concomitant increase in the number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact nervous system, TOM-1 negatively regulates synaptic vesicle priming. This paper examines the in vivo role of the syntaxin binding protein tomosyn in synaptic transmission at the C. elegans neuromuscular junction. Tomosyn inhibits vesicle priming by regulating the size of the readily releasable vesicle pool.