EPHA介导的生长锥塌陷
中文名称
通路描述
EPH/Ephrin信号与Rho家族GTP酶如Rac、Rho和Cdc42偶联，这些酶连接双向受体 - 配体相互作用到细胞骨架的变化（Noren & Pasquale 2004, Groeger & Nobes 2007）。RHOA调节细胞骨架动力学，参与EPH诱导的生长锥塌陷。这通过ephexins介导。ephexins是Rho GTP酶的GTP交换因子，与EPH激酶结构域相互作用，其后续激活不同地影响Rho GTP酶，使得RHOA被激活，而Cdc42和Rac1被抑制。RHOA的激活和Cdc42、Rac的抑制将细胞骨架转向收缩增加和扩张减少，导致生长锥塌陷（Shamah et al. 2001, Sahin et al. 2005）。在生长的神经元中，EPH受体的激活通常导致生长锥塌陷反应并从表达ephrin的基底上退缩（Poliakov et al. 2004, Pasquale 2005）。EPH介导的排斥反应防止轴突向过度表达ephrin的区域生长，例如上丘的后端（Pasquale 2005）。
英文描述
EPHA-mediated growth cone collapse EPH/Ephrin signaling is coupled to Rho family GTPases such as Rac, Rho and Cdc42 that connect bidirectional receptor-ligand interactions to changes in the actin cytoskeleton (Noren & Pasquale 2004, Groeger & Nobes 2007). RHOA regulates actin dynamics and is involved in EPHA-induced growth cone collapse. This is mediated by ephexins. Ephexin, a guanine nucleotide exchange factor for Rho GTPases, interacts with the EPHA kinase domain and its subsequent activation differentially affects Rho GTPases, such that RHOA is activated, whereas Cdc42 and Rac1 are inhibited. Activation of RHOA, and inhibition of Cdc42 and Rac, shifts actin cytoskeleton to increased contraction and reduced expansion leading to growth-cone collapse (Shamah et al. 2001, Sahin et al. 2005). The activation of EPH receptors in growing neurons typically, but not always, leads to a growth cone collapse response and retraction from an ephrin-expressing substrate (Poliakov et al. 2004, Pasquale 2005). EPHA-mediated repulsive responses prevent axons from growing into regions of excessive ephrin-A concentration, such as the posterior end of the superior colliculus (Pasquale 2005).
所含基因
29 个基因