Pak functions downstream of dock to regulate photoreceptor axon guidance in Drosophila
Pak functions downstream of dock to regulate photoreceptor axon guidance in Drosophila
复制标题
DOI：
10.1016/s0092-8674(00)80798-9
复制
发表时间：
1999-06-25
期刊：
影响因子：
64.5
通讯作者：
Zipursky, SL
中科院分区：
文献类型：
--
作者：
Hing, H;Xiao, J;Zipursky, SL
SH2/SH3 接头蛋白 Dock 已被提议将信号从引导受体转导至果蝇感光器（R 细胞）生长锥中的肌动蛋白细胞骨架。在这里，我们证明果蝇 p21 激活激酶 (Pak) 在调节 R 细胞轴突引导和靶向的 Dock 通路中是必需的。 Dock 和 Pak 共定位于 R 细胞轴突和生长锥，发生物理相互作用，并且它们的功能丧失表型无法区分。 R 细胞连接的正常模式需要 Pak 的激酶活性以及 Dock 和 Cdc42/Rac 的结合位点。 Pak (Pak(myr)) 的膜束缚形式充当主要的功能获得蛋白。 Pak(myr) 的视网膜表达可挽救码头突变体中的 R 细胞连接表型。这些数据表明 Pak 是体内轴突引导的关键调节剂和 Dock 的下游效应器。
The SH2/SH3 adaptor protein Dock has been proposed to transduce signals from guidance receptors to the actin cytoskeleton in Drosophila photoreceptor (R cell) growth cones. Here, we demonstrate that Drosophila p21-activated kinase (Pak) is required in a Dock pathway regulating R cell axon guidance and targeting. Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable. Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac. A membrane-tethered form of Pak (Pak(myr)) acts as a dominant gain-of-function protein. Retinal expression of Pak(myr) rescues the R cell connectivity phenotype in dock mutants. These data establish Pak as a critical regulator of axon guidance and a downstream effector of Dock in vivo.