Cell：控制大脑发育的关键基因

据刊登在9月4日Cell杂志的封面文章，北卡罗莱纳大学的研究人员现在发现，大脑发育形成神经网络的过程中，大量的神经元必须要迁移到正确的位置，并与周围神经元构成复杂的突触连接。一旦该过程出错，则会导致精神发育迟滞，诵读困难，自闭症等精神障碍。

之前的研究认为，细胞形变或移动是通过细胞骨架活动形成的。但该研究结果表明，大脑发育过程中脑蛋白srGAP2可以直接通过弯曲细胞膜，使细胞发生形变形成丝状伪足(filopodia)。但这种srGAP2蛋白是出现在3p-综合症(3p- syndrome)的蛋白质家族的一员。因此，该研究或许对研究这类精神障碍疾病具有重要意义。

srGAP2基因在大脑发育过程中一直处于活跃表达状态，srGAP2蛋白存在一个独特的结构域——F-BAR域。研究人员利用电流在小鼠大脑切片导入能控制srGAP2蛋白F-BAR域活性的遗传物质。然后培养并观察脑神经元的动态。当激活F-BAR域时，研究人员发现神经元形成阻止迁移的丝状伪足。而当减少该蛋白的表达水平时，神经元迁移的速度加快，分支减少。

据研究人员介绍，srGAP2蛋白F-BAR域与神经元的分支数量密切相关，这些分支是神经元之间相互联系必要结构。 (生物谷Bioon.com)

生物谷推荐原始出处：

Cell, Volume 138, Issue 5, 990-1004, 4 September 2009 doi:10.1016/j.cell.2009.06.047

The F-BAR Domain of srGAP2 Induces Membrane Protrusions Required for Neuronal Migration and Morphogenesis

Sabrice Guerrier1,2,Jaeda Coutinho-Budd3,Takayuki Sassa2,Aurélie Gresset1,Nicole Vincent Jordan1,Keng Chen4,Wei-Lin Jin4,Adam Frost5,6andFranck Polleux1,2,,

1 Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2 Neuroscience Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3 Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4 Institute of Neurosciences, Shanghai Jiao Tong University, Shanghai 200240, China
5 Department of Molecular Biophysics and Biochemistry, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06510, USA

During brain development, proper neuronal migration and morphogenesis is critical for the establishment of functional neural circuits. Here we report that srGAP2 negatively regulates neuronal migration and induces neurite outgrowth and branching through the ability of its F-BAR domain to induce filopodia-like membrane protrusions resembling those induced by I-BAR domains invivo and invitro. Previous work has suggested that in nonneuronal cells filopodia dynamics decrease the rate of cell migration and the persistence of leading edge protrusions. srGAP2 knockdown reduces leading process branching and increases the rate of neuronal migration invivo. Overexpression of srGAP2 or its F-BAR domain has the opposite effects, increasing leading process branching and decreasing migration. These results suggest that F-BAR domains are functionally diverse and highlight the functional importance of proteins directly regulating membrane deformation for proper neuronal migration and morphogenesis.