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肌动蛋白结合蛋白调控γ-神经元的轴突生长和分支。

Cofilin regulates axon growth and branching of γ-neurons.

机构信息

Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel.

Department of Molecular Cell Biology, Weizmann Institute of Sciences, Rehovot 7610001, Israel

出版信息

J Cell Sci. 2020 Apr 28;133(8):jcs232595. doi: 10.1242/jcs.232595.

Abstract

The mechanisms that control intrinsic axon growth potential, and thus axon regeneration following injury, are not well understood. Developmental axon regrowth of mushroom body γ-neurons during neuronal remodeling offers a unique opportunity to study the molecular mechanisms controlling intrinsic growth potential. Motivated by the recently uncovered developmental expression atlas of γ-neurons, we here focus on the role of the actin-severing protein cofilin during axon regrowth. We show that Twinstar (Tsr), the fly cofilin, is a crucial regulator of both axon growth and branching during developmental remodeling of γ-neurons. mutant axons demonstrate growth defects both and , and also exhibit actin-rich filopodial-like structures at failed branch points Our data is inconsistent with Tsr being important for increasing G-actin availability. Furthermore, analysis of microtubule localization suggests that Tsr is required for microtubule infiltration into the axon tips and branch points. Taken together, we show that Tsr promotes axon growth and branching, likely by clearing F-actin to facilitate protrusion of microtubules.

摘要

控制内在轴突生长潜力的机制,以及损伤后轴突再生的机制,尚不完全清楚。在神经元重塑过程中,蘑菇体γ-神经元的发育性轴突再生为研究控制内在生长潜力的分子机制提供了一个独特的机会。受最近发现的γ-神经元发育表达图谱的启发,我们在此关注肌动蛋白切割蛋白丝切蛋白(Cofilin)在轴突再生中的作用。我们发现,Twinstar(Tsr),即果蝇丝切蛋白,是γ-神经元发育重塑过程中轴突生长和分支的关键调节因子。Tsr 突变体的轴突表现出生长缺陷,和 ,并且在失败的分支点也表现出富含肌动蛋白的丝状伪足样结构。我们的数据与 Tsr 对增加 G-肌动蛋白可用性很重要的观点不一致。此外,对微管定位的分析表明,Tsr 对于微管渗透到轴突尖端和分支点是必需的。综上所述,我们表明 Tsr 促进轴突生长和分支,可能是通过清除 F-肌动蛋白来促进微管的突起。

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