Siah Regulation of Pard3A Controls Neuronal Cell Adhesion During Germinal Zone Exit
Siah Regulation of Pard3A Controls Neuronal Cell Adhesion During Germinal Zone Exit
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DOI：
10.1126/science.1198480
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发表时间：
2010-12-23
期刊：
影响因子：
56.9
通讯作者：
Solecki, David J.
中科院分区：
文献类型：
--
作者：
Famulski, Jakub K.;Trivedi, Niraj;Solecki, David J.
大脑的回路是通过发育过程中神经元的定向迁移和突触发生建立的。尽管神经元以特定的模式成熟和迁移，但人们对神经元如何退出其生发区生态位知之甚少。我们发现，小脑颗粒神经元生发区出口调节蛋白酶体降解Pard 3A的七缺席同源物（Siah）E3泛素连接酶。Pard 3A功能的获得和Siah功能的丧失导致过早的径向迁移。使用探针测量神经元细胞接触的延时成像显示，Pard 3A通过将上皮紧密连接粘附分子C募集到神经元细胞表面来促进生发带退出所需的粘附相互作用。我们的研究结果定义了Siah-Pard 3A信号通路，该通路控制神经元祖细胞或未成熟神经元从生发区小生境的粘附依赖性退出。
The brain's circuitry is established by directed migration and synaptogenesis of neurons during development. Although neurons mature and migrate in specific patterns, little is known about how neurons exit their germinal zone niche. We found that cerebellar granule neuron germinal zone exit is regulated by proteasomal degradation of Pard3A by the Seven in Absentia homolog (Siah) E3 ubiquitin ligase. Pard3A gain of function and Siah loss of function induce precocious radial migration. Time-lapse imaging using a probe to measure neuronal cell contact reveals that Pard3A promotes adhesive interactions needed for germinal zone exit by recruiting the epithelial tight junction adhesion molecule C to the neuronal cell surface. Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche.