Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain
Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain
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DOI：
10.1083/jcb.201704071
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发表时间：
2018-01-01
影响因子：
7.8
通讯作者：
Kessels, Michael M.
中科院分区：
文献类型：
--
作者：
Izadi, Maryam;Schlobinski, Dirk;Kessels, Michael M.
局部肌动蛋白丝的形成为神经元的信号接收乔木的发育提供动力，所述神经元的信号接收乔木是神经元网络形成的基础。然而，我们对驱动这些过程的分子知之甚少，并且可能在功能上将它们与在形成树突状乔木的受限区域中观察到的瞬时钙脉冲联系起来。在这里，我们证明，蓝带（Cobl）样，一个未表征的蛋白质，建议代表一个非常遥远的相关，进化的祖先的肌动蛋白成核剂Cobl，尽管只有一个单一的G-肌动蛋白结合Wiskott-Aldrich综合征蛋白同源2（WH 2）域，大规模促进形成的F-肌动蛋白丰富的膜皱褶的COS-7细胞和神经元的树突状分支。Cobl-like因此将WH 2结构域功能与F-肌动蛋白结合蛋白Abp 1的功能整合。Cobl样介导的树突状分支依赖于Abp 1以及Ca 2 +/钙调蛋白（CaM）信号传导和CaM缔合。钙信号传导促进与Cobl-like辅因子Abp 1的复合物形成。因此，Ca 2 +/CaM控制肌动蛋白动力学似乎是一个更广泛使用的原则，在细胞生物学比以前认为的。
Local actin filament formation powers the development of the signal-receiving arbor of neurons that underlies neuronal network formation. Yet, little is known about the molecules that drive these processes and may functionally connect them to the transient calcium pulses observed in restricted areas in the forming dendritic arbor. Here we demonstrate that Cordon-Bleu (Cobl)-like, an uncharacterized protein suggested to represent a very distantly related, evolutionary ancestor of the actin nucleator Cobl, despite having only a single G-actin-binding Wiskott-Aldrich syndrome protein Homology 2 (WH2) domain, massively promoted the formation of F-actin-rich membrane ruffles of COS-7 cells and of dendritic branches of neurons. Cobl-like hereby integrates WH2 domain functions with those of the F-actin-binding protein Abp1. Cobl-like-mediated dendritic branching is dependent on Abp1 as well as on Ca2+/calmodulin (CaM) signaling and CaM association. Calcium signaling leads to a promotion of complex formation with Cobl-like's cofactor Abp1. Thus, Ca2+/CaM control of actin dynamics seems to be a much more broadly used principle in cell biology than previously thought.