EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin
EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin
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DOI：
10.1016/s0092-8674(01)00314-2
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发表时间：
2001-04-20
期刊：
影响因子：
64.5
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Shamah, SM;Lin, MZ;Greenberg, ME
Eph 受体通过调节生长锥内的肌动蛋白动力学来转导短程排斥信号以引导轴突。我们报告了 ephexin 的克隆和表征，ephexin 是一种新型 Eph 受体相互作用蛋白，是 Rho GTPases 鸟嘌呤核苷酸交换因子 (GEF) Dbl 家族的成员。 Ephrin-A 刺激 EphA 受体可调节 ephexin 的活性，导致 RhoA 激活、Cdc42 和 Rac1 抑制以及细胞形态变化。此外，原代神经元中 ephexin 突变体的表达会干扰 ephrin-A 诱导的生长锥塌陷。 ephexin 与 Eph 受体的结合构成了 Eph 受体和肌动蛋白细胞骨架之间的分子联系，并为实现生长锥运动的高度局部调节提供了新的机制。
Eph receptors transduce short-range repulsive signals for axon guidance by modulating actin dynamics within growth cones. We report the cloning and characterization of ephexin, a novel Eph receptor-interacting protein that is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Ephrin-A stimulation of EphA receptors modulates the activity of ephexin leading to RhoA activation, Cdc42 and Rac1 inhibition, and cell morphology changes. In addition, expression of a mutant form of ephexin in primary neurons interferes with ephrin-A-induced growth cone collapse. The association of ephexin with Eph receptors constitutes a molecular link between Eph receptors and the actin cytoskeleton and provides a novel mechanism for achieving highly localized regulation of growth cone motility.