CD47 promotes neuronal development through Src- and FRG/Vav2-mediated activation of Rac and Cdc42
CD47 promotes neuronal development through Src- and FRG/Vav2-mediated activation of Rac and Cdc42
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DOI：
10.1523/jneurosci.3981-06.2006
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发表时间：
2006-11-29
影响因子：
5.3
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
--
作者：
Murata, Takaaki;Ohnishi, Hiroshi;Matozaki, Takashi
轴突和树突的发育是由Rho家族的小GTP结合蛋白控制的，但负责这种调节的上游信号机制仍不清楚。我们现在已经研究了跨膜蛋白分化簇47（CD 47）在海马神经元这一过程中的作用。CD 47缺陷的神经元表现出明显受损的树突和轴突的发展，而过度表达的CD 47促进这种发展。含SH 2结构域的蛋白酪氨酸磷酸酶底物-1（SHPS-1）与CD 47的相互作用也诱导了树突状丝状伪足和棘的形成。CD 47的这些作用通过抑制细胞分裂周期42（Cdc 42）或Rac来防止。在CD 47缺陷的神经元中，Src的自磷酸化显著减少。此外，CD 47的过表达促进Src的自磷酸化。Src家族激酶的抑制确实阻止了CD 47促进的树突发育。FGD 1相关Cdc 42-鸟嘌呤核苷酸交换因子（GEF）（FRG）或Vav 2（Cdc 42和Rac的GEF，由Src激活）的抑制也阻止了CD 47对树突发育的影响。这些结果表明，CD 47促进海马神经元中树突和轴突的发育，其方式至少部分依赖于Src以及FRG和Vav 2介导的Cdc 42和Rac的激活。
The development of axons and dendrites is controlled by small GTP-binding proteins of the Rho family, but the upstream signaling mechanisms responsible for such regulation remain unclear. We have now investigated the role of the transmembrane protein cluster of differentiation 47 (CD47) in this process with hippocampal neurons. CD47-deficient neurons manifested markedly impaired development of dendrites and axons, whereas overexpression of CD47 promoted such development. Interaction of SH2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) with CD47 also induced the formation of dendritic filopodia and spines. These effects of CD47 were prevented by inhibition of either cell division cycle 42 (Cdc42) or Rac. In CD47-deficient neurons, autophosphorylation of Src was markedly reduced. In addition, overexpression of CD47 promoted the autophosphorylation of Src. Inhibition of Src family kinases indeed prevented CD47-promoted dendritic development. Inhibition of either FGD1- related Cdc42-guanine nucleotide exchange factor (GEF) (FRG) or Vav2, which is a GEF for Cdc42 and Rac and is activated by Src, also prevented the effects of CD47 on dendritic development. These results indicate that CD47 promotes development of dendrites and axons in hippocampal neurons in a manner dependent, at least in part, on activation of Cdc42 and Rac mediated by Src as well as by FRG and Vav2.