Erbin controls dendritic morphogenesis by regulating localization of δ-catenin
Erbin controls dendritic morphogenesis by regulating localization of δ-catenin
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DOI：
10.1523/jneurosci.0451-08.2008
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发表时间：
2008-07-09
影响因子：
5.3
通讯作者：
Reichardt, Louis F.
中科院分区：
文献类型：
--
作者：
Arikkath, Jyothi;Israely, Inbal;Reichardt, Louis F.
富含亮氨酸和突触后密度-95/椎间盘大/闭合性突触蛋白-1（PDZ）蛋白erbin和δ-连环蛋白（钙粘蛋白-连环蛋白细胞粘附复合物的一种组分）在神经元中高度表达，并通过PDZ介导的相互作用相关联，但神经元功能的特征不完全。我们发现短发夹RNA介导的erbin基因敲低和delta-catenin基因敲低或基因消融严重损害了海马神经元树突的形态发生。erbin和δ-连环蛋白的同时缺失不会增加这种表型的严重性。erbin缺失后观察到的树突状表型通过δ-连环蛋白的过表达而被拯救，并且需要δ-连环蛋白中的一个结构域，该结构域已被证明可调节树突状分支。delta-catenin的敲低不能通过erbin的过表达来挽救，表明erbin在delta-catenin的上游。δ-连环蛋白缺失神经元的活性Rac 1/RhoA的整体水平没有改变。erbin的敲低导致δ-连环蛋白定位的改变。这些结果表明，erbin在调节树突状细胞形态发生的关键作用，保持适当的本地化的δ-连环蛋白。
The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and delta-catenin, a component of the cadherin-catenin cell adhesion complex, are highly expressed in neurons and associate through PDZ-mediated interaction, but have incompletely characterized neuronal functions. We show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic ablation of delta-catenin severely impaired dendritic morphogenesis in hippocampal neurons. Simultaneous loss of erbin and delta-catenin does not enhance severity of this phenotype. The dendritic phenotype observed after erbin depletion is rescued by overexpression of delta-catenin and requires a domain in delta-catenin that has been shown to regulate dendritic branching. Knockdown of delta-catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of delta-catenin. delta-Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in localization of delta-catenin. These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of delta-catenin.