Septin-driven coordination of actin and microtubule remodeling regulates the collateral branching of axons.

Septin-driven coordination of actin and microtubule remodeling regulates the collateral branching of axons.
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DOI:
10.1016/j.cub.2012.04.019
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发表时间:
2012-06-19
期刊:
影响因子:
9.2
通讯作者:
Spiliotis, Elias T.
Spiliotis, Elias T.
中科院分区:
生物学1区
文献类型:
--
作者:
Hu, Jianli;Bai, Xiaobo;Bowen, Jonathan R.;Dolat, Lee;Korobova, Farida;Yu, Wenqian;Baas, Peter W.;Svitkina, Tatyana;Gallo, Gianluca;Spiliotis, Elias T.

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轴突分支是外周和中枢神经系统发育的基础。从轴突轴长出的分支称为侧支或间质支。轴突的侧支需要由肌动蛋白微丝(F-actin)形成丝状伪足,并且它们与从轴突轴张开的微管(MT)一起充血。在分支形态发生过程中驱动和协调肌动蛋白和MT重塑的机制还知之甚少。Septins是GTP结合蛋白的一个家族,它可以寡聚成与细胞膜、肌动蛋白和微管细胞骨架相关的高级结构。在这里,我们表明,侧支轴突需要SEPT 6和SEPT 7,两个相互作用的septins。在感觉神经元的轴突中,SEPT 6和SEPT 7都积聚在丝状伪足形成的初始位点。我们发现,SEPT 6定位于轴突补丁的F-肌动蛋白,并增加招聘的corneum,Arp 2/3介导的肌动蛋白聚合的调节,触发出现丝状伪足。相反,SEPT 7促进轴突MT进入丝状伪足,从而形成侧支。令人惊讶的是,septins通过协调肌动蛋白和微管细胞骨架的重塑为轴突的侧支分支提供了一种新的机制。
Axon branching is fundamental to the development of the peripheral and central nervous system. Branches that sprout from the axon shaft are termed collateral or interstitial branches. Collateral branching of axons requires the formation of filopodia from actin microfilaments (F-actin) and their engorgement with microtubules (MTs) that splay from the axon shaft. The mechanisms that drive and coordinate the remodeling of actin and MTs during branch morphogenesis are poorly understood. Septins comprise a family of GTP-binding proteins that oligomerize into higher order structures, which associate with membranes and the actin and microtubule cytoskeleton. Here, we show that collateral branching of axons requires SEPT6 and SEPT7, two interacting septins. In the axons of sensory neurons, both SEPT6 and SEPT7 accumulate at incipient sites of filopodia formation. We show that SEPT6 localizes to axonal patches of F-actin and increases the recruitment of cortactin, a regulator of Arp2/3-mediated actin polymerization, triggering the emergence of filopodia. Conversely, SEPT7 promotes the entry of axonal MTs into filopodia, enabling the formation of collateral branches. Surprisingly, septins provide a novel mechanism for the collateral branching of axons by coordinating the remodeling of the actin and microtubule cytoskeleton.
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