p120 Catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins
p120 Catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins
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DOI：
10.1016/j.neuron.2006.05.018
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发表时间：
2006-07-06
期刊：
影响因子：
16.2
通讯作者：
Reichardt, Louis F.
中科院分区：
文献类型：
--
作者：
Elia, Lisa P.;Yamamoto, Miya;Reichardt, Louis F.
钙黏蛋白 - 连环蛋白复合物和Rho家族GTP酶都已被证明可调节树突发育。我们在此表明p120连环蛋白（p120ctn）在调节发育中的小鼠大脑的棘突和突触形成中具有作用。体内海马锥体神经元中p120连环蛋白基因缺失导致沿树突的棘突和突触密度降低。此外，p120连环蛋白缺失导致钙黏蛋白水平降低以及Rho家族GTP酶调节异常，Rac1活性降低且RhoA活性增加。体外分析表明，棘突密度降低反映了Rho家族GTP酶信号传导异常，而对棘突成熟的影响似乎是由钙黏蛋白水平降低以及可能的Rho家族GTP酶信号传导异常导致的。因此，p120ctn作为钙黏蛋白和Rho家族GTP酶之间的信号协调者，调节棘突和突触发育过程中所需的细胞骨架变化。
Both the cadherin-catenin complex and Rho-family GTPases have been shown to regulate dendrite development. We show here a role for p120 catenin (p120ctn) in regulating spine and synapse formation in the developing mouse brain. p120catenin gene deletion in hippocampal pyramidal neurons in vivo resulted in reduced spine and synapse densities along dendrites. In addition, p120 catenin loss resulted in reduced cadherin levels and misregulation of Rho-family GTPases, with decreased Rac1 and increased RhoA activity. Analyses in vitro indicate that the reduced spine density reflects aberrant Rho-family GTPase signaling, whereas the effects on spine maturation appear to result from reduced cadherin levels and possibly aberrant Rho-family GTPase signaling. Thus, p120ctn acts as a signal coordinator between cadherins and Rho-family GTPases to regulate cytoskeletal changes required during spine and synapse development.