Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Cell Biol. 2010 Nov 29;191(5):1013-27. doi: 10.1083/jcb.201006006. Epub 2010 Nov 22.
Recent studies in Drosophila have implicated actin cytoskeletal remodeling in myoblast fusion, but the cellular mechanisms underlying this process remain poorly understood. Here we show that actin polymerization occurs in an asymmetric and cell type-specific manner between a muscle founder cell and a fusion-competent myoblast (FCM). In the FCM, a dense F-actin-enriched focus forms at the site of fusion, whereas a thin sheath of F-actin is induced along the apposing founder cell membrane. The FCM-specific actin focus invades the apposing founder cell with multiple finger-like protrusions, leading to the formation of a single-channel macro fusion pore between the two muscle cells. Two actin nucleation-promoting factors of the Arp2/3 complex, WASP and Scar, are required for the formation of the F-actin foci, whereas WASP but not Scar promotes efficient foci invasion. Our studies uncover a novel invasive podosome-like structure (PLS) in a developing tissue and reveal a previously unrecognized function of PLSs in facilitating cell membrane juxtaposition and fusion.
最近在果蝇中的研究表明，肌动蛋白细胞骨架重塑在成肌细胞融合中起作用，但这一过程的细胞机制仍知之甚少。在这里，我们发现肌原祖细胞和成肌融合细胞（FCM）之间的肌动蛋白聚合以不对称和细胞类型特异性的方式发生。在 FCM 中，在融合部位形成密集的富含 F-肌动蛋白的焦点，而在相邻的肌原祖细胞膜上诱导形成薄的 F-肌动蛋白鞘。FCM 特异性的肌动蛋白焦点通过多个指状突起侵入相邻的肌原祖细胞，导致两个肌肉细胞之间形成单通道大融合孔。Arp2/3 复合物的两个肌动蛋白成核促进因子 WASP 和 Scar 对于 F-肌动蛋白焦点的形成是必需的，而 WASP 但不是 Scar 促进有效的焦点入侵。我们的研究揭示了在发育组织中存在一种新的侵袭性足状伪足样结构（PLS），并揭示了 PLS 在促进细胞膜并置和融合方面的先前未被认识到的功能。
