Branched actin polymerization drives invasive protrusion formation to promote myoblast fusion during skeletal muscle regeneration

• DOI: 10.7554/elife.103550.1
• Publication Date: 2025-01-03T18:25:20Z
• Authors: Yue Lu; Tezin Walji; Pratima Pandey; Chuanli Zhou; Christa W Habela; Scott B Snapper; Rong Li; Elizabeth H Chen

Skeletal muscle regeneration is a multistep process involving the activation, proliferation, differentiation, and fusion of stem cells, known as satellite cells. The s atellite c ell-derived mononucleated m uscle cells (SCMs) indispensable for generation multinucleated, contractile myofibers during repair. However, molecular cellular mechanisms underlying SCM remain poorly understood. In this study, we uncovered an essential role branched actin polymerization in fusion. Using conditional knockouts Arp2/3 complex its nucleation-promoting factors, N-WASP WAVE, demonstrated that required fusion, but not cell migration. We showed WAVE complexes have partially redundant functions regulating Furthermore, generating invasive protrusions at fusogenic synapses SCMs. Taken together, our study has identified new components myoblast machinery skeletal critical actin-propelled process.