Reelin signals through apolipoprotein E receptor 2 and Cdc42 to increase growth cone motility and filopodia formation.
Reelin signals through apolipoprotein E receptor 2 and Cdc42 to increase growth cone motility and filopodia formation.
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DOI：
10.1523/jneurosci.4036-10.2010
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发表时间：
2010-11-03
期刊：
影响因子：
--
通讯作者：
Bock HH
中科院分区：
文献类型：
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作者：
Leemhuis J;Bouché E;Frotscher M;Henle F;Hein L;Herz J;Meyer DK;Pichler M;Roth G;Schwan C;Bock HH
脂蛋白受体信号调节有丝分裂后神经元在发育过程中的定位和分化，并调节成熟大脑中神经元的可塑性。根据上下文情况，脂蛋白受体配体Reelin可以对皮质神经元产生相反的作用。我们发现Reelin增加了生长锥的运动和丝状足的形成，并确定了潜在的信号级联。Reelin以Apoer2-， Disabled-1-和磷脂酰肌醇3-激酶依赖的方式激活Rho GTPase Cdc42，以其在神经元形态发生和定向迁移中的作用而闻名。我们证明了神经元囊泡运输，一个cdc42控制的过程，在Reelin治疗后增加，并进一步提供了肽能VIP/ pacap38系统和Reelin可以在功能上相互作用以促进轴突分支。综上所述，reelin诱导的Cdc42激活有助于调节单个响应神经元的细胞骨架，并与其他信号级联融合，协调Rho GTPase活性，促进神经元发育。我们的数据表明Rho GTPases和Reelin信号的缺陷是导致神经和精神疾病的发育缺陷的原因。
Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an Apoer2-, Disabled-1- and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/PACAP38-system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders.