Complexin has opposite effects on two modes of synaptic vesicle fusion.
Complexin has opposite effects on two modes of synaptic vesicle fusion.
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DOI：
10.1016/j.cub.2010.12.014
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发表时间：
2011-01-25
期刊：
影响因子：
9.2
通讯作者：
Dittman, Jeremy S.
中科院分区：
文献类型：
--
作者：
Martin, Jesse A.;Hu, Zhitao;Fenz, Katherine M.;Fernandez, Joel;Dittman, Jeremy S.
突触传递可以以二元或分级的方式发生，这取决于递质释放是由动作电位触发还是由膜电位的逐渐变化触发。这两种类型的融合事件的分子差异及其在生理背景下的差异调节尚未得到解决。复合蛋白是一种保守的SNARE结合蛋白，被认为可以调节自发和刺激诱发的突触囊泡（SV）融合。在这里，我们研究复杂的功能，在一个分级突触在C。优雅的。尽管神经系统功能显著受损，但神经复合蛋白（cpx-1）突变体是可行的。CPX-1的缺失导致神经肌肉接头处的强直性突触传递速率增加3倍，而刺激诱发的SV融合降低10倍。缺失其C-末端结构域的截短的CPX-1可以拯救刺激诱发的突触囊泡胞吐，但不能抑制紧张性活动，表明这两种胞吐模式可以在分子水平上区分。具有受损的SNARE结合的CPX-1变体也挽救了诱发的但不是紧张性的神经递质释放。最后，通过去除CPX-1，可以在突触融合蛋白点突变体中拯救强直性而非诱发性释放。救援任何形式的胞吐部分恢复运动行为，表明这两种类型的突触传递是相关的。这些观察结果表明CPX-1的双重作用：抑制由低水平内源性神经活动驱动的SV胞吐，同时促进由去极化刺激驱动的SV的同步融合。因此，突触活动的模式调节复合蛋白在分级突触中的抑制和允许作用。
Synaptic transmission can occur in a binary or graded fashion depending on whether transmitter release is triggered by action potentials or by gradual changes in membrane potential. Molecular differences of these two types of fusion events and their differential regulation in a physiological context have yet to be addressed. Complexin is a conserved SNARE-binding protein that has been proposed to regulate both spontaneous and stimulus-evoked synaptic vesicle (SV) fusion. Here, we examine complexin function at a graded synapse in C. elegans. Null complexin (cpx-1) mutants are viable although nervous system function is significantly impaired. Loss of CPX-1 results in a 3-fold increase in the rate of tonic synaptic transmission at the neuromuscular junction while stimulus-evoked SV fusion is decreased 10-fold. A truncated CPX-1 missing its C-terminal domain can rescue stimulus-evoked synaptic vesicle exocytosis but fails to suppress tonic activity, demonstrating that these two modes of exocytosis can be distinguished at the molecular level. A CPX-1 variant with impaired SNARE-binding also rescues evoked but not tonic neurotransmitter release. Finally, tonic but not evoked release can be rescued in a syntaxin point mutant by removing CPX-1. Rescue of either form of exocytosis partially restores locomotory behavior indicating that both types of synaptic transmission are relevant. These observations suggest a dual role for CPX-1: suppressing SV exocytosis driven by low levels of endogenous neural activity while promoting synchronous fusion of SVs driven by a depolarizing stimulus. Thus, patterns of synaptic activity regulate complexin's inhibitory and permissive roles at a graded synapse.
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DOI：
10.1126/science.1166500
发表时间：
2009-01-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Giraudo CG;Garcia-Diaz A;Eng WS;Chen Y;Hendrickson WA;Melia TJ;Rothman JE
通讯作者：
Rothman JE
DOI：
10.1098/rspb.1967.0010
发表时间：
1967-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KATZ, B;MILEDI, R
通讯作者：
MILEDI, R
DOI：
10.1523/jneurosci.0378-08.2008
发表时间：
2008-07-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dittman JS;Kaplan JM
通讯作者：
Kaplan JM
影响因子：
25
作者：
Huntwork, Sarah;Littleton, J. Troy
通讯作者：
Littleton, J. Troy
影响因子：
16.2
作者：
Nurrish, S;Ségalat, L;Kaplan, JM
通讯作者：
Kaplan, JM