Hamp Julia, Löwer Andreas, Dottermusch-Heidel Christine, Beck Lothar, Moussian Bernard, Flötenmeyer Matthias, Önel Susanne-Filiz
Philipps-Universität Marburg, FB Biologie, Entwicklungsbiologie, Karl-von-Frisch Str. 8, Marburg 35043, Germany.
Fachbereich Biologie, Spezielle Zoologie, Philipps-Universität Marburg, Karl-von-Frisch Str. 8, Marburg 35043, Germany.
J Cell Sci. 2016 Sep 15;129(18):3426-36. doi: 10.1242/jcs.175638. Epub 2016 Aug 12.
The fusion of founder cells and fusion-competent myoblasts (FCMs) is crucial for muscle formation in Drosophila Characteristic events of myoblast fusion include the recognition and adhesion of myoblasts, and the formation of branched F-actin by the Arp2/3 complex at the site of cell-cell contact. At the ultrastructural level, these events are reflected by the appearance of finger-like protrusions and electron-dense plaques that appear prior to fusion. Severe defects in myoblast fusion are caused by the loss of Kette (a homolog of Nap1 and Hem-2, also known as NCKAP1 and NCKAP1L, respectively), a member of the regulatory complex formed by Scar or WAVE proteins (represented by the single protein, Scar, in flies). kette mutants form finger-like protrusions, but the electron-dense plaques are extended. Here, we show that the electron-dense plaques in wild-type and kette mutant myoblasts resemble other electron-dense structures that are known to function as cellular junctions. Furthermore, analysis of double mutants and attempts to rescue the kette mutant phenotype with N-cadherin, wasp and genes of members of the regulatory Scar complex revealed that Kette has two functions during myoblast fusion. First, Kette controls the dissolution of electron-dense plaques. Second, Kette controls the ratio of the Arp2/3 activators Scar and WASp in FCMs.
在果蝇中,原始细胞与具有融合能力的成肌细胞(FCM)的融合对于肌肉形成至关重要。成肌细胞融合的特征性事件包括成肌细胞的识别与黏附,以及在细胞 - 细胞接触位点由Arp2/3复合物形成分支状F - 肌动蛋白。在超微结构水平上,这些事件表现为在融合之前出现的指状突起和电子致密斑。成肌细胞融合的严重缺陷是由Kette(分别是Nap1和Hem - 2的同源物,也分别称为NCKAP1和NCKAP1L)缺失引起的,Kette是由Scar或WAVE蛋白(在果蝇中由单一蛋白Scar代表)形成的调节复合物的成员。kette突变体形成指状突起,但电子致密斑延长。在这里,我们表明野生型和成肌细胞突变体中的电子致密斑类似于已知作为细胞连接起作用的其他电子致密结构。此外,对双突变体的分析以及用N - 钙黏着蛋白、WASP和调节性Scar复合物成员的基因挽救kette突变体表型的尝试表明,Kette在成肌细胞融合过程中具有两种功能。第一,Kette控制电子致密斑的溶解。第二,Kette控制FCM中Arp2/3激活剂Scar和WASP的比例。