Saarikangas Juha, Hakanen Janne, Mattila Pieta K, Grumet Martin, Salminen Marjo, Lappalainen Pekka
Program in Cellular Biotechnology, Institute of Biotechnology, University of Helsinki, Finland.
J Cell Sci. 2008 May 1;121(Pt 9):1444-54. doi: 10.1242/jcs.027466. Epub 2008 Apr 14.
Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATP-actin monomers with high affinity and deforms PtdIns(4,5)P(2)-rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins.
放射状胶质细胞在中枢神经系统发育过程中的神经元迁移、轴突导向和神经发生中发挥关键作用。然而,调节这些伸展细胞生长和形态的分子机制尚不清楚。我们发现,ABBA是IRSp53-MIM蛋白家族的一个新成员,在不同类型的放射状胶质细胞中富集。ABBA分别通过其WH2和IM结构域,以高亲和力结合ATP-肌动蛋白单体,并在体外使富含磷脂酰肌醇(4,5)二磷酸(PtdIns(4,5)P(2))的膜变形。在放射状胶质细胞样C6-R细胞中,ABBA定位于肌动蛋白细胞骨架和质膜之间的界面,RNA干扰使其缺失导致片状伪足动力学和突起延伸出现缺陷。总之,本研究确定ABBA是放射状胶质细胞中肌动蛋白和质膜动力学的新型调节因子,并提供证据表明膜结合和变形活性对IRSp53-MIM-ABBA家族蛋白的细胞功能至关重要。