Function of the Drosophila receptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance

Function of the Drosophila receptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance
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DOI:
10.1242/dev.095968
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发表时间:
2014-01-01
期刊:
影响因子:
4.6
通讯作者:
Kolodkin, Alex L.
Kolodkin, Alex L.
中科院分区:
生物学2区
文献类型:
--
作者:
Chak, Kayam;Kolodkin, Alex L.

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第二信使cAMP和cGMP调节由神经元引导线索介导的吸引和排斥。我们发现果蝇受体鸟苷酸环化酶Gyc 76 C与Semaphorin 1a(Sema-1a)发生遗传相互作用,并与Sema-1a受体丛蛋白A(PlexA)发生物理联系。PlexA在体外调节Gyc 76 C催化活性,并且每个不同的Gyc 76 C蛋白结构域对于在体外调节Gyc 76 C活性和在体内运动轴突引导是至关重要的。胞浆蛋白dGIPC与Gyc 76 C相互作用,并促进Sema-1a-PlexA/Gyc 76 C介导的运动轴突导向。这些发现提供了一个在体内的联系,脑信号蛋白介导的排斥性轴突的指导和细胞内神经元cGMP水平的改变。
The second messengers cAMP and cGMP modulate attraction and repulsion mediated by neuronal guidance cues. We find that the Drosophila receptor guanylyl cyclase Gyc76C genetically interacts with Semaphorin 1a (Sema-1a) and physically associates with the Sema-1a receptor plexin A (PlexA). PlexA regulates Gyc76C catalytic activity in vitro, and each distinct Gyc76C protein domain is crucial for regulating Gyc76C activity in vitro and motor axon guidance in vivo. The cytosolic protein dGIPC interacts with Gyc76C and facilitates Sema-1a-PlexA/Gyc76C-mediated motor axon guidance. These findings provide an in vivo link between semaphorin-mediated repulsive axon guidance and alteration of intracellular neuronal cGMP levels.