A Presynaptic Role for the Cytomatrix Protein GIT in Synaptic Vesicle Recycling
A Presynaptic Role for the Cytomatrix Protein GIT in Synaptic Vesicle Recycling
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DOI：
10.1016/j.celrep.2014.04.051
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发表时间：
2014-06-12
期刊：
影响因子：
8.8
通讯作者：
Haucke, Volker
中科院分区：
文献类型：
--
作者：
Podufall, Jasmin;Tian, Rui;Haucke, Volker
神经传递涉及神经末梢突触囊泡（SVs）的外吞循环。胞吐是由聚集在活性区（AZ）的细胞基质促进的。胞外SV在AZ膜上的融合与胞内SV的回收之间确切的空间和功能关系尚不清楚。在这里，我们发现支架G蛋白偶联受体激酶2相互作用（GIT）蛋白是az相关细胞基质的一个组成部分，并作为SV内吞作用的调节因子。研究表明，GIT1及其同源基因dGIT与内吞受体stonin2 / stonineb直接相关。在果蝇dGIT突变体中，stonineb和synaptotagmin水平降低，stonineb部分错位。此外，dgit突变体在SV循环中表现出形态和功能缺陷。这些数据证实了GIT在SV循环中的突触前作用，并表明AZ细胞基质与内吞机制之间存在联系。
Neurotransmission involves the exo-endocytic cycling of synaptic vesicles (SVs) within nerve terminals. Exocytosis is facilitated by a cytomatrix assembled at the active zone (AZ). The precise spatial and functional relationship between exocytic fusion of SVs at AZ membranes and endocytic SV retrieval is unknown. Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix and as a regulator of SV endocytosis. GIT1 and its D. melanogaster ortholog, dGIT, are shown to directly associate with the endocytic adaptor stonin 2/stoned B. In Drosophila dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is partially mislocalized. Moreover, dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling and suggest a connection between the AZ cytomatrix and the endocytic machinery.