Control of axonal branching and synapse formation by focal adhesion kinase
Control of axonal branching and synapse formation by focal adhesion kinase
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DOI：
10.1038/nn1317
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发表时间：
2004-10-01
影响因子：
25
通讯作者：
Reichardt, LF
中科院分区：
文献类型：
--
作者：
Rico, B;Beggs, HE;Reichardt, LF
中枢神经系统（CNS）神经元网络的形成需要精确控制轴突分支的发育和稳定。在这里，我们表明，细胞特异性消融小鼠基因Ptk2（通常称为fak），编码局灶黏附激酶（fak），增加体内神经元形成的轴突终末和突触的数量。与此一致的是，fak突变神经元在培养中也形成了更多的轴突分支，因为它们增加了分支的形成，减少了分支的收缩。野生型FAK的表达，而不是阻止与Rho家族gtpase调节因子（包括p190Rho鸟嘌呤核交换因子（p190RhoGEF））相互作用的几种FAK变体的表达，挽救了FAK突变神经元中观察到的轴突树木化表型。此外，不能与FAK相关的p190RhoGEF突变体的表达导致与缺乏FAK的神经元非常相似的表型。因此，FAK作为轴突分支和突触形成的负调节因子，并且似乎部分通过Rho家族GTPases发挥其作用。
The formation of neuronal networks in the central nervous system (CNS) requires precise control of axonal branch development and stabilization. Here we show that cell-specific ablation of the murine gene Ptk2 (more commonly known as fak), encoding focal adhesion kinase (FAK), increases the number of axonal terminals and synapses formed by neurons in vivo. Consistent with this, fak mutant neurons also form greater numbers of axonal branches in culture because they have increased branch formation and reduced branch retraction. Expression of wild-type FAK, but not that of several FAK variants that prevent interactions with regulators of Rho family GTPases including the p190 Rho guanine nuclear exchange factor (p190RhoGEF), rescues the axonal arborization phenotype observed in fak mutant neurons. In addition, expression of a mutant p190RhoGEF that cannot associate with FAK results in a phenotype very similar to that of neurons lacking FAK. Thus, FAK functions as a negative regulator of axonal branching and synapse formation, and it seems to exert its actions, in part, through Rho family GTPases.