Mechanism, control and cellular functions of Cobl-mediated actin nucleation

复杂肌动蛋白超结构的形成对于所有真核生物的生命都是必不可少的，但因此严重依赖于促进第一个肌动蛋白单体组装的因素的帮助，这一过程称为成核。尽管形成了丰富的不同的肌动蛋白结构，只有两类这样的肌动蛋白成核因子是很好地建立在高等真核生物中，Arp 2/3复合物和formin。与Cobl，我们最近已经确定了一种新的和非常强大的肌动蛋白成核剂的适当的神经形态，属于新的WH 2域为基础的成核剂类必不可少的。我们希望我们的全面研究不仅能让我们解开Cobl控制肌动蛋白细胞骨架的详细分子机制，而且还能更深入地了解高等真核生物的不同肌动蛋白超结构是如何形成的，以及它们如何支持它们所参与的细胞过程的巨大多样性。Cobl蛋白相互作用的鉴定和功能表征，这可能控制肌动蛋白成核的这种新的强大机制的活性和/或亚细胞定位，将显着增加我们对神经形态发生和神经元网络形成的基础肌动蛋白细胞骨架过程的分子理解-对所有高等真核生物的生命至关重要的功能。

The formation of complex actin superstructures is indispensable for life of all eukaryotes but thereby critically relies on the help of factors facilitating the assembly of the first actin monomers, a process termed nucleation. Despite the wealth of different actin structures formed, only two classes of such actin nucleation factors are well established in higher eukaryotes, the Arp2/3 complex and formins. With Cobl, we have recently identified a novel and very powerful actin nucleator indispensable for proper neuromorphogenesis that belongs to the new class of WH2 domain-based nucleators. We expect that our comprehensive studies will not only allow us to unravel the detailed molecular mechanism by which Cobl controls the actin cytoskeleton but will furthermore lead to deeper insights into how the different actin superstructures of higher eukaryotes are formed and how they support the huge diversity of cellular processes they are involved in. The identification and functional characterization of Cobl protein interactions, which may control the activity and/or the subcellular localization of this novel powerful machinery for actin nucleation, will significantly increase our molecular understanding of the actin cytoskeletal processes underlying neuromorphogenesis and the formation of neuronal networks – functions crucial for life of all higher eukaryotes.