Signalling and crosstalk of Rho GTPases in mediating axon guidance
Signalling and crosstalk of Rho GTPases in mediating axon guidance
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DOI：
10.1038/ncb895
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发表时间：
2003
影响因子：
21.3
通讯作者：
Xiao-Bing Yuan;M. Jin;Xiaohua Xu;Yuan-quan Song;Chien-ping Wu;M. Poo;S. Duan
中科院分区：
文献类型：
--
作者：
Xiao-Bing Yuan;M. Jin;Xiaohua Xu;Yuan-quan Song;Chien-ping Wu;M. Poo;S. Duan
神经系统发育过程中轴突的伸展受多种因素的影响，但触发轴突伸展的信号机制大多尚不清楚。在这里，我们研究了Rho家族小鸟苷三磷酸酶(GTP酶)在弥散因子介导轴突导向中的作用。在不显著影响丝孔形成和轴突延伸的浓度下，在培养的非洲爪哇脊髓神经元中表达显性负性或结构性活性的CDC42，可以消除由脑源性神经营养因子诱导的趋化生长锥体转向，该梯度可以激活培养神经元中的CDC42和RAC。溶血磷脂酸的梯度诱导的化学排斥也被显性-负性RhoA的表达所消除。我们还表明，Rho激酶或丝状突起穿过生长锥的不对称性足以触发转向反应，并且在CDC42和RhoA通路之间存在串扰，这是通过它们对生长锥化学排斥所必需的肌球蛋白活性的汇聚作用来实现的。
Axon extension during development of the nervous system is guided by many factors, but the signalling mechanisms responsible for triggering this extension remain mostly unknown. Here we have examined the role of Rho family small guanosine triphosphatases (GTPases) in mediating axon guidance by diffusible factors. Expression of either dominant-negative or constitutively active Cdc42 in culturedXenopus laevisspinal neurons, at a concentration that does not substantially affect filopodial formation and neurite extension, abolishes the chemoattractive growth cone turning induced by a gradient of brain-derived neurotrophic factor that can activate Cdc42 and Rac in cultured neurons. Chemorepulsion induced by a gradient of lysophosphatidic acid is also abolished by the expression of dominant-negative RhoA. We also show that an asymmetry in Rho kinase or filopodial initiation across the growth cone is sufficient to trigger the turning response and that there is a crosstalk between the Cdc42 and RhoA pathways through their converging actions on the myosin activity essential for growth cone chemorepulsion.