Dock4 regulates dendritic development in hippocampal neurons
Dock4 regulates dendritic development in hippocampal neurons
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DOI：
10.1002/jnr.21763
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发表时间：
2008-11
影响因子：
4.2
通讯作者：
Shuhei Ueda;S. Fujimoto;Kiyo Hiramoto;M. Negishi;H. Katoh
中科院分区：
文献类型：
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作者：
Shuhei Ueda;S. Fujimoto;Kiyo Hiramoto;M. Negishi;H. Katoh
树突发育是建立适当的神经元连接所必需的。Rho家族小GTP酶在树突状细胞的生长和形态调控中起重要作用。然而，控制Rho GTP酶在树突发育中的活性的分子机制还不清楚。在本研究中，我们发现Dock4，一个小的GTTRAC的激活剂，在调节大鼠海马神经元树突的生长和分支中发挥作用。Dock4在发育中的大鼠脑中高度表达，主要在海马神经元中。在分离培养的海马神经元中，Dock4蛋白的表达在培养3至8天后上调，此时树突开始生长。内源性Dock4的敲低导致树突生长和分支减少。相反，Dock4与其结合伴侣ELMO2的过表达增加了树突和树突分支的数量。由Dock4和ELMO2引起的这些形态学效应需要Rac活化和Dock4的C末端Crk结合区。事实上，Dock4在海马神经元中与ELMO 2和CrkII形成复合物。这些发现证明了Rac激活剂Dock 4在海马神经元树枝状形态发生中的新功能。© 2008 Wiley利斯公司
Dendrite development is required for establishing proper neuronal connectivity. Rho‐family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up‐regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C‐terminal Crk‐binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley‐Liss, Inc.