Guerrier Sabrice, Coutinho-Budd Jaeda, Sassa Takayuki, Gresset Aurélie, Jordan Nicole Vincent, Chen Keng, Jin Wei-Lin, Frost Adam, Polleux Franck
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell. 2009 Sep 4;138(5):990-1004. doi: 10.1016/j.cell.2009.06.047.
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 in vivo and in vitro. 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 in vivo. 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.
在大脑发育过程中，适当的神经元迁移和形态发生对于功能性神经回路的建立至关重要。在此我们报告，srGAP2通过其F-BAR结构域诱导丝状伪足样膜突出的能力，在体内和体外负向调节神经元迁移，并诱导神经突生长和分支，这种膜突出类似于由I-BAR结构域诱导的膜突出。先前的研究表明，在非神经元细胞中，丝状伪足动态变化会降低细胞迁移速率和前沿突出的持续性。在体内，敲低srGAP2可减少领先突起分支并增加神经元迁移速率。过表达srGAP2或其F-BAR结构域则具有相反的效果，增加领先突起分支并降低迁移速率。这些结果表明，F-BAR结构域在功能上具有多样性，并突出了直接调节膜变形的蛋白质对于适当的神经元迁移和形态发生的功能重要性。
