Heterotrimeric G-protein, Gi1, is involved in the regulation of proliferation, neuronal migration and dendrite morphology during cortical development in vivo.
Heterotrimeric G-protein, Gi1, is involved in the regulation of proliferation, neuronal migration and dendrite morphology during cortical development in vivo.
复制标题
异三聚体 G 蛋白 (Gi1) 参与体内皮质发育过程中增殖、神经元迁移和树突形态的调节。
DOI：
10.1111/jnc.15205
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Nagata K.
中科院分区：
文献类型：
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作者：
Hamada N;Iwamoto I;Kawamura N;Nagata K.
异源三聚体G蛋白由α、β和γ亚基组成，并作为信号转导子发挥作用。迄今为止，已经报道了Gi/o家族异源三聚体G蛋白Gαi2和Gα o 1的α亚基在脑发育和神经发育障碍中的关键作用。在本研究中，我们试图阐明另一个Gi/o家族成员Gi 1的α-亚基Gαi1在皮质生成中的作用，基于最近在神经发育障碍中发现的基因异常。在蛋白质印迹分析中，发现Gαi1以发育阶段依赖性方式在小鼠脑中表达。形态学分析显示，Gαi1在胚胎14天的大脑皮层中广泛分布，在脑室区（VZ）表达相对较高。同时，Gαi1在E14时在VZ和边缘区的尚未鉴定的早期有丝分裂细胞的膜区域中富集。在子宫电穿孔的大脑皮层中，Gαi1的急性敲低引起神经前体细胞的细胞周期延长并促进其细胞周期退出。Gαi1缺陷的皮质神经元在皮质发生过程中也表现出延迟的径向迁移，异常延长的前导过程和核分裂障碍。此外，Gαi1的沉默阻止了基底树突的发育。迁移和树突状表型至少部分地被Gαi1的RNAi抗性版本拯救。总的来说，这些结果强烈表明，Gi 1在皮质发育中的关键作用，其功能的干扰可能会导致突触网络形成的缺陷，导致神经发育障碍。
Heterotrimeric G‐proteins are composed of α, β, and γ subunits, and function as signal transducers. Critical roles of the α‐subunits of Gi/o family heterotrimeric G‐proteins, Gαi2, and Gαo1, have so far been reported in brain development and neurodevelopmental disorders. In this study, we tried to clarify the role of Gαi1, α‐subunit of another Gi/o family member Gi1, during corticogenesis, based on the recent identification of its gene abnormalities in neurodevelopmental disorders. In western blot analyses, Gαi1 was found to be expressed in mouse brain in a developmental stage‐dependent manner. Morphological analyses revealed that Gαi1 was broadly distributed in cerebral cortex with relatively high expression in the ventricular zone (VZ) at embryonic day (E) 14. Meanwhile, Gαi1 was enriched in membrane area of yet unidentified early mitotic cells in the VZ and the marginal zone at E14. Acute knockdown of Gαi1 within uteroelectroporation in cerebral cortex caused cell cycle elongation of the neural progenitor cells and promoted their cell cycle exit. Gαi1‐deficient cortical neurons also exhibited delayed radial migration during corticogenesis, with abnormally elongated leading processes and hampered nucleokinesis. In addition, silencing of Gαi1 prevented basal dendrite development. The migration and dendritic phenotypes were at least partially rescued by an RNAi‐resistant version of Gαi1. Collectively, these results strongly suggest a crucial role of Gi1 in cortical development, and disturbance of its function may cause deficits in synaptic network formation, leading to neurodevelopmental disorders.