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微管正端蛋白EB3对F-肌动蛋白结合蛋白drebrin的靶向作用是神经突形成所必需的。

Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis.

作者信息

Geraldo Sara, Khanzada Umme K, Parsons Maddy, Chilton John K, Gordon-Weeks Phillip R

机构信息

The MRC Centre for Developmental Neurobiology, New Hunt's House, Guy's Campus, King's College London, London SE11UL, UK.

出版信息

Nat Cell Biol. 2008 Oct;10(10):1181-9. doi: 10.1038/ncb1778. Epub 2008 Sep 21.

Abstract

Interactions between dynamic microtubules and actin filaments (F-actin) underlie a range of cellular processes including cell polarity and motility. In growth cones, dynamic microtubules are continually extending into selected filopodia, aligning alongside the proximal ends of the F-actin bundles. This interaction is essential for neuritogenesis and growth-cone pathfinding. However, the molecular components mediating the interaction between microtubules and filopodial F-actin have yet to be determined. Here we show that drebrin, an F-actin-associated protein, binds directly to the microtubule-binding protein EB3. In growth cones, this interaction occurs specifically when drebrin is located on F-actin in the proximal region of filopodia and when EB3 is located at the tips of microtubules invading filopodia. When this interaction is disrupted, the formation of growth cones and the extension of neurites are impaired. We conclude that drebrin targets EB3 to coordinate F-actin-microtubule interactions that underlie neuritogenesis.

摘要

动态微管与肌动蛋白丝(F-肌动蛋白)之间的相互作用是一系列细胞过程的基础,包括细胞极性和运动性。在生长锥中,动态微管不断延伸至选定的丝状伪足中,沿F-肌动蛋白束的近端排列。这种相互作用对神经突发生和生长锥路径寻找至关重要。然而,介导微管与丝状伪足F-肌动蛋白之间相互作用的分子成分尚未确定。在此我们表明,一种与F-肌动蛋白相关的蛋白 drebrin 直接与微管结合蛋白EB3结合。在生长锥中,当drebrin位于丝状伪足近端区域的F-肌动蛋白上且EB3位于侵入丝状伪足的微管尖端时,这种相互作用特异性发生。当这种相互作用被破坏时,生长锥的形成和神经突的延伸会受损。我们得出结论,drebrin 将EB3作为靶点来协调神经突发生所依赖的F-肌动蛋白-微管相互作用。

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