Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins).
Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins).
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DOI：
10.1523/jneurosci.0416-12.2012
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发表时间：
2012-07-04
期刊：
影响因子：
--
通讯作者：
Prokop A
中科院分区：
文献类型：
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作者：
Alves-Silva J;Sánchez-Soriano N;Beaven R;Klein M;Parkin J;Millard TH;Bellen HJ;Venken KJ;Ballestrem C;Kammerer RA;Prokop A
轴突的正确生长对神经系统的发育和再生至关重要。轴突生长主要由微管驱动。在这种情况下，微管的关键调节因子是spectraplakins，一个进化上保守的肌动蛋白-微管连接子家族。小鼠spectraplakin ACF 7或其接近的果蝇同源物Short stop/Shot的功能丧失同样会导致严重的轴突缩短和微管紊乱。spectraplakins如何执行这些功能尚不清楚。在这里，我们表明，轴突生长促进作用的镜头需要相互作用与EB 1（端结合蛋白）在聚合加端微管。我们发现，结合的镜头EB 1需要SxIP图案在镜头的羧基末端尾（Ctail），这些图案的突变废除镜头功能轴突生长，EB 1功能表型的损失镜头损失，和遗传相互作用的研究揭示了强大的功能之间的联系，镜头和EB 1在轴突生长和微管组织。此外，我们报告说，拍摄本地化沿着微管轴和稳定他们对水诱导解聚。该功能是EB 1独立的，但需要Ctail内的净正电荷，这基本上有助于Shot的微管轴缔合。因此，spectraplakins是两类重要的神经元微管调节蛋白的真正成员：+TIP（加上末端调节剂）和结构MAP（微管相关蛋白）。从我们的数据中，我们推导出一个模型，涉及到不同的功能的spectraplakin羧基末端的两个功能的轴突生长过程中拍摄。
The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close Drosophila homologue Short stop/Shot similarly cause severe axon shortening and microtubule disorganisation. How spectraplakins perform these functions is not known. Here we show that axonal growth promoting roles of Shot require interaction with EB1 (End binding protein) at polymerising plus ends of microtubules. We show that binding of Shot to EB1 requires SxIP motifs in Shot’s carboxyterminal tail (Ctail), mutations of these motifs abolish Shot functions in axonal growth, loss of EB1 function phenocopies Shot loss, and genetic interaction studies reveal strong functional links between Shot and EB1 in axonal growth and microtubule organisation. In addition, we report that Shot localises along microtubule shafts and stabilises them against pharmacologically induced depolymerisation. This function is EB1-independent but requires net positive charges within Ctail which essentially contribute to the microtubule shaft association of Shot. Therefore, spectraplakins are true members of two important classes of neuronal microtubule regulating proteins: +TIPs (plus end regulators) and structural MAPs (microtubule associated proteins). From our data we deduce a model that relates the different features of the spectraplakin carboxy-terminus to the two functions of Shot during axonal growth.