The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I
The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I
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DOI：
10.1038/emboj.2011.207
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发表时间：
2011-08-03
期刊：
影响因子：
11.4
通讯作者：
Qualmann, Britta
中科院分区：
文献类型：
--
作者：
Schwintzer, Lukas;Koch, Nicole;Qualmann, Britta
皮质肌动蛋白成核的空间控制对于细胞形态的正确建立和可塑性是必不可少的。 Cobl 是一种新型的基于 WH2 结构域的肌动蛋白成核剂。然而，Cobl 成核活性的细胞协调仍然难以捉摸。在这里，我们揭示了 Cobl 的细胞功能依赖于 syndapin。 Cobl/syndapin 复合物在体内形成，如共定位、共免疫沉淀和亚细胞募集研究所证明。体外重构和亚细胞分级分离表明，通过其脂质结合 Fer/CIP4 同源 (FCH)-Bin/Amphiphyn/Rvs (F-BAR) 结构域，syndapin 将 Cobl 招募到膜上。一致地，syndapin I RNAi 损害 Cobl 的皮质定位。神经元的进一步功能研究表明，Cobl 和 syndapin I 在树突乔木发育中协同作用。重要的是，这两种蛋白质对于树突发生都至关重要。 Cobl 介导的神经形态发生功能主要依赖于 syndapin I，有趣的是还依赖于 Arp3。共免疫沉淀证明，内源性 Cobl、syndapin I 和 Arp2/3 复合物激活剂以及 Syndapin 结合伴侣 N-WASP 存在于一种复合物中。总之，这些数据提供了对 Cobl 介导功能的分子基础的详细见解，并揭示了不同的肌动蛋白成核剂在神经形态发生过程中与 Syndapin I 功能性地交织在一起。 EMBO 杂志 (2011) 30, 3147-3159。 doi：10.1038/emboj.2011.207； 2011 年 7 月 1 日在线发布
Spatial control of cortical actin nucleation is indispensable for proper establishment and plasticity of cell morphology. Cobl is a novel WH2 domain-based actin nucleator. The cellular coordination of Cobl's nucleation activity, however, has remained elusive. Here, we reveal that Cobl's cellular functions are dependent on syndapin. Cobl/syndapin complexes form in vivo, as demonstrated by colocalization, coimmunoprecipitation and subcellular recruitment studies. In vitro reconstitutions and subcellular fractionations demonstrate that, via its lipid-binding Fer/CIP4 Homology (FCH)-Bin/Amphiphysin/Rvs (F-BAR) domain, syndapin recruits Cobl to membranes. Consistently, syndapin I RNAi impairs cortical localization of Cobl. Further functional studies in neurons show that Cobl and syndapin I work together in dendritic arbor development. Importantly, both proteins are crucial for dendritogenesis. Cobl-mediated functions in neuromorphogenesis critically rely on syndapin I and interestingly also on Arp3. Endogenous Cobl, syndapin I and the Arp2/3 complex activator and syndapin-binding partner N-WASP were present in one complex, as demonstrated by coimmunoprecipitations. Together, these data provide detailed insights into the molecular basis for Cobl-mediated functions and reveal that different actin nucleators are functionally intertwined by syndapin I during neuromorphogenesis. The EMBO Journal (2011) 30, 3147-3159. doi:10.1038/emboj.2011.207; Published online 1 July 2011