Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development.
Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development.
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DOI：
10.7554/elife.67718
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发表时间：
2021-07-15
期刊：
影响因子：
7.7
通讯作者：
Kessels MM
中科院分区：
文献类型：
--
作者：
Izadi M;Seemann E;Schlobinski D;Schwintzer L;Qualmann B;Kessels MM
局部肌动蛋白丝的形成对于神经元树突突的发育是必不可少的。我们发现，令人惊讶的是，单个肌动蛋白丝促进因子的作用不足以为树突发生提供动力。相反，这需要肌动蛋白成核子Cobl和它唯一的进化远祖Cobl-样相互依赖地作用。Cobl-like和Cobl之间的这种协调是通过合成蛋白的物理连接实现的。Syndapin I在突起结构底部的凸面质膜区域形成纳米结构域，并与cobllike中的三个基序相互作用，其中一个基序是Ca2+/钙调素调节的。一致地，syndapin I， cob -like新发现的N端钙调蛋白结合位点和单一的Ca2+/钙调蛋白响应syndapin结合基元都对cob -like的功能至关重要。因此，在树突乔木发育中，局部Ca2+/ cam控制的肌动蛋白动力学依赖于不同的f -肌动蛋白形成促进因子的调节和物理协调的相互作用，只有在一起，它们才有能力带来哺乳动物神经网络形成所需的复杂神经元形态。
Local actin filament formation is indispensable for development of the dendritic arbor of neurons. We show that, surprisingly, the action of single actin filament-promoting factors was insufficient for powering dendritogenesis. Instead, this required the actin nucleator Cobl and its only evolutionary distant ancestor Cobl-like acting interdependently. This coordination between Cobl-like and Cobl was achieved by physical linkage by syndapins. Syndapin I formed nanodomains at convex plasma membrane areas at the base of protrusive structures and interacted with three motifs in Cobl-like, one of which was Ca2+/calmodulin-regulated. Consistently, syndapin I, Cobl-like’s newly identified N terminal calmodulin-binding site and the single Ca2+/calmodulin-responsive syndapin-binding motif all were critical for Cobl-like’s functions. In dendritic arbor development, local Ca2+/CaM-controlled actin dynamics thus relies on regulated and physically coordinated interactions of different F-actin formation-promoting factors and only together they have the power to bring about the sophisticated neuronal morphologies required for neuronal network formation in mammals.