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

Yue Lu; Tezin Walji; Pratima Pandey; Chuanli Zhou; Christa W. Habela; Scott B. Snapper; Rong Li; Elizabeth H. Chen

doi:10.7554/eLife.103550.4.sa4

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

Journal article

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

Yue Lu, Tezin Walji, Pratima Pandey, Chuanli Zhou, Christa W. Habela, Scott B. Snapper, Rong Li and Elizabeth H. Chen

eLife, Vol.14, 103550

01/29/2026

DOI: 10.7554/eLife.103550.4.sa4

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Abstract

Skeletal muscle regeneration is a multistep process involving the activation, proliferation, differentiation, and fusion of muscle stem cells, known as satellite cells. Fusion of satellite cell-derived myoblasts (SCMs) is indispensable for generating the multinucleated, contractile myofibers during muscle repair. However, the molecular and cellular mechanisms underlying SCM fusion during muscle regeneration remain incompletely understood. Here, we reveal a critical role for branched actin polymerization in SCM fusion during mouse skeletal muscle regeneration. Using conditional knockouts of the Arp2/3 complex and its actin nucleation-promoting factors N-WASP and WAVE, we demonstrate that branched actin polymerization is specifically required for SCM fusion but dispensable for satellite cell proliferation, differentiation, and migration. We show that the N-WASP and WAVE complexes have partially redundant functions in regulating SCM fusion and that branched actin polymerization is essential for generating invasive protrusions at fusogenic synapses in SCMs. Together, our study identifies branched-actin regulators as key components of the myoblast fusion machinery and establishes invasive protrusion formation as a critical mechanism enabling myoblast fusion during skeletal muscle regeneration.

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Title: Subtitle: Branched actin polymerization drives invasive protrusion formation to promote myoblast fusion during mouse skeletal muscle regeneration
Creators: Yue Lu - The University of Texas Southwestern Medical Center
Tezin Walji - The University of Texas Southwestern Medical Center
Pratima Pandey - The University of Texas Southwestern Medical Center
Chuanli Zhou - The University of Texas Southwestern Medical Center
Christa W. Habela - Johns Hopkins University
Scott B. Snapper - Boston Children's Hospital
Rong Li - Johns Hopkins University
Elizabeth H. Chen - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: eLife, Vol.14, 103550
DOI: 10.7554/eLife.103550.4.sa4
ISSN: 2050-084X
eISSN: 2050-084X
Publisher: eLIFE SCIENCES PUBL LTD
Number of pages: 18
Grant note: 10.58275/aha.25cda1451113.pc.gr.229681 / American Heart Association R35GM136316 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
Language: English
Date published: 01/29/2026
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9985150289302771

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