Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming
Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming
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DOI：
10.1016/s0896-6273(01)00272-0
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发表时间：
2001-04-01
期刊：
影响因子：
16.2
通讯作者：
Brose, N
中科院分区：
文献类型：
--
作者：
Betz, A;Thakur, P;Brose, N
突触神经递质的释放被限制在活动区，在那里突触小泡拴系、启动融合能力和钙离子触发的融合过程以高度协调的方式发生。我们证明了活动区成分Munc13-1和RIM1在功能上相互作用。Munc13-1是一种必需的囊泡启动蛋白，RIM1是一种可能在囊泡拴系中发挥作用的Rab3效应器。这种相互作用的破坏会导致具有融合能力的突触小泡的丧失，产生Munc13-1缺陷神经元的表型。RIM1结合和囊泡启动是由Munc13-1的两个不同的结构模块介导的。Munc13-1/RIM1相互作用可能在突触小泡拴系和启动之间建立功能联系，或者它可能调节启动反应本身，从而决定具有融合能力的小泡的数量。
Synaptic neurotransmitter release is restricted to active zones, where the processes of synaptic vesicle tethering, priming to fusion competence, and Ca2+-triggered fusion are taking place in a highly coordinated manner, We show that the active zone components Munc13-1, an essential vesicle priming protein, and RIM1, a Rab3 effector with a putative role in vesicle tethering, interact functionally. Disruption of this interaction causes a loss of fusion-competent synaptic vesicles, creating a phenocopy of Munc13-1-deficient neurons. RIM1 binding and Vesicle priming are mediated by two distinct structural modules of Munc13-1. The Munc13-1/RIM1 interaction may create a functional link between synaptic vesicle tethering and priming, or it may regulate the priming reaction itself, thereby determining the number of fusion-competent vesicles.