WASP and SCAR have distinct roles in activating the Arp2/3 complex during myoblast fusion
WASP and SCAR have distinct roles in activating the Arp2/3 complex during myoblast fusion
复制标题
DOI：
10.1242/jcs.022269
复制
发表时间：
2008-04-15
影响因子：
4
通讯作者：
Oenel, Susanne-Filiz
中科院分区：
文献类型：
--
作者：
Berger, Susanne;Schaefer, Gritt;Oenel, Susanne-Filiz
哺乳动物和果蝇的成肌细胞融合分两步进行。首先，创始细胞（FCs）和融合能力强的成肌细胞（fcm）融合形成三核前体，然后再招募更多的fcm。这一过程依赖于融合受限的肌原粘连结构（FuRMAS）的形成，该结构在细胞接触部位含有丝状肌动蛋白（f -肌动蛋白）栓。融合依赖于HEM2 （NAP1）同源物Kette，以及Blow和WASP （Wiskott-Aldrich-syndrome蛋白家族的一员）。在这里，我们展示了一个新的Arp3-null等位基因schwachling的鉴定和特征。超微结构分析表明，Arp3（schwachling）突变体可以形成融合孔，但不能整合融合的FCM。双突变体实验显示，Arp3和黄蜂双突变体的融合被完全阻断，这表明还有一个F-actin调节因子参与其中。事实上，scar/WAVE和与wasp相互作用的伙伴vrp1 (sltr, wip)/ wip的双突变分析表明，f -肌动蛋白调节因子scar也控制成肌细胞融合过程中f -肌动蛋白的形成。此外，在Arp3黄蜂和疤痕vrp1双突变体中观察到的协同表型表明，wasp和scar在控制F-actin形成方面具有不同的作用。根据这些发现，我们推导了成肌细胞融合过程中肌动蛋白调节的新模型。
Myoblast fusion takes place in two steps in mammals and in Drosophila. First, founder cells (FCs) and fusion-competent myoblasts (FCMs) fuse to form a trinucleated precursor, which then recruits further FCMs. This process depends on the formation of the fusion-restricted myogenic-adhesive structure (FuRMAS), which contains filamentous actin (F-actin) plugs at the sites of cell contact. Fusion relies on the HEM2 (NAP1) homolog Kette, as well as Blow and WASP, a member of the Wiskott-Aldrich-syndrome protein family. Here, we show the identification and characterization of schwachling - a new Arp3-null allele. Ultrastructural analyses demonstrate that Arp3(schwachling) mutants can form a fusion pore, but fail to integrate the fusing FCM. Double-mutant experiments revealed that fusion is blocked completely in Arp3 and wasp double mutants, suggesting the involvement of a further F-actin regulator. Indeed, double-mutant analyses with scar/WAVE and with the WASP-interacting partner vrp1 (sltr, wip)/WIP show that the F-actin regulator scar also controls F-actin formation during myoblast fusion. Furthermore, the synergistic phenotype observed in Arp3 wasp and in scar vrp1 double mutants suggests that WASP and SCAR have distinct roles in controlling F-actin formation. From these findings we derived a new model for actin regulation during myoblast fusion.