Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton.
Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton.
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DOI：
10.1083/jcb.201110127
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发表时间：
2012-04-02
期刊：
影响因子：
--
通讯作者：
Colón-Ramos DA
中科院分区：
文献类型：
--
作者：
Stavoe AK;Colón-Ramos DA
已知在神经元引导期间组织肌动蛋白细胞骨架的信号模块也在突触组装期间指示突触囊泡聚集。Netrin是一种化学营养因子，已知可调节许多神经发育过程，包括细胞迁移、轴突导向和突触发生。虽然Netrin在突触发生中的作用在整个进化过程中是保守的，但它指导突触组装的机制尚不清楚。在这里，我们确定了一种机制，其中Netrin受体β-40/DCC指示突触囊泡在体内聚类。β-40定位于突触前区域，以响应Netrin。我们发现，ESTA-40与CED-5/DOCK 180相互作用，并指导CED-5突触前定位。CED-5又通过CED-10/Rac 1和CET-10/Lamellipodin发出信号，以组织突触前区域的肌动蛋白细胞骨架。这一信号通路的突触前区域的本地化是必要的突触组装过程中的突触囊泡集群，但不是活性区蛋白的亚细胞定位。因此，囊泡聚集和活性区蛋白的定位由Netrin下游的单独途径指示。我们的数据表明，已知的组织肌动蛋白细胞骨架在指导过程中的信号模块可以增选，以指导突触囊泡集群。
A signaling module known to organize the actin cytoskeleton during neuronal guidance also instructs synaptic vesicle clustering during synapse assembly. Netrin is a chemotrophic factor known to regulate a number of neurodevelopmental processes, including cell migration, axon guidance, and synaptogenesis. Although the role of Netrin in synaptogenesis is conserved throughout evolution, the mechanisms by which it instructs synapse assembly are not understood. Here we identify a mechanism by which the Netrin receptor UNC-40/DCC instructs synaptic vesicle clustering in vivo. UNC-40 localized to presynaptic regions in response to Netrin. We show that UNC-40 interacted with CED-5/DOCK180 and instructed CED-5 presynaptic localization. CED-5 in turn signaled through CED-10/Rac1 and MIG-10/Lamellipodin to organize the actin cytoskeleton in presynaptic regions. Localization of this signaling pathway to presynaptic regions was necessary for synaptic vesicle clustering during synapse assembly but not for the subcellular localization of active zone proteins. Thus, vesicle clustering and localization of active zone proteins are instructed by separate pathways downstream of Netrin. Our data indicate that signaling modules known to organize the actin cytoskeleton during guidance can be co-opted to instruct synaptic vesicle clustering.
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