Cdc42和RhoA可介导细胞外因子对轴突的吸引及排斥作用

被引：0

作者：

袁小兵

机构：

[1] 中国科学院研究生院（上海脑研究所）

关键词：

轴突导向; Rho family GTPase; 细胞骨架; BDNF; LPA; ryanodine; ROCK; MLCK;

D O I：

暂无

年度学位：

2001

学位类型：

博士

导师：

蒲慕明; 段树民; 吴建屏;

摘要：

本实验研究了两种Rho GTPases在可溶性因子诱导的轴突生长锥转向中所起的作用。在培养的爪蟾胚胎脊髓神经元中表达显性失活突变型(dominant negative, DN)或组成性激活突变型(constitutively active, CA) Cdc42能够阻断脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的浓度梯度对轴突生长锥的化学吸引作用。溶血磷脂酸(lysophosphatidic acid,LPA)的浓度梯度造成的生长锥排斥反应在神经元内表达DN-RhoA后被阻断,表达CA-Cdc42则使之转化为吸引反应。在PKA受抑制的情况下,BDNF诱导的轴突排斥反应在表达DN-Cdc42或DN-RhoA后被逆转为吸引反应。进一步用Rho kinase抑制剂及MLCK抑制剂进行的实验证明,Cdc42与RhoA信号通路都能够在生长锥转向中起指令性作用,且这两条通路能够部分汇聚于肌球蛋白II ( myosin II )并由肌球蛋白介导生长锥的排斥反应。

引用

页数：107

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