Huang Zhiyu, Yazdani Umar, Thompson-Peer Katherine L, Kolodkin Alex L, Terman Jonathan R
Center for Basic Neuroscience, Department of Pharmacology, NA4.301/5323 Harry Hines Blvd, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Development. 2007 Jun;134(12):2337-47. doi: 10.1242/dev.004242.
Members of the Cas family of Src homology 3 (SH3)-domain-containing cytosolic signaling proteins are crucial regulators of actin cytoskeletal dynamics in non-neuronal cells; however, their neuronal functions are poorly understood. Here, we identify a Drosophila Cas (DCas), find that Cas proteins are highly expressed in neurons and show that DCas is required for correct axon guidance during development. Functional analyses reveal that Cas specifies axon guidance by regulating the degree of fasciculation among axons. These guidance defects are similar to those observed in integrin mutants, and genetic analysis shows that integrins function together with Cas to facilitate axonal defasciculation. These results strongly support Cas proteins working together with integrins in vivo to direct axon guidance events.
含有Src同源3（SH3）结构域的胞质信号蛋白Cas家族成员是非神经元细胞中肌动蛋白细胞骨架动力学的关键调节因子；然而，它们在神经元中的功能却知之甚少。在这里，我们鉴定出一种果蝇Cas（DCas），发现Cas蛋白在神经元中高度表达，并表明DCas是发育过程中正确轴突导向所必需的。功能分析表明，Cas通过调节轴突之间的成束程度来指定轴突导向。这些导向缺陷与整合素突变体中观察到的缺陷相似，遗传分析表明整合素与Cas共同发挥作用以促进轴突解束。这些结果有力地支持了Cas蛋白在体内与整合素共同作用来指导轴突导向事件。
