CKIP-1 regulates mammalian and zebrafish myoblast fusion.

Equipe Différenciation Neuromusculaire, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5239/ENS Lyon, Université de Lyon, IFR128 Biosciences Lyon-Gerland, 46 Allée d'Italie, 69364 LYON cedex 07, France.
Journal of Cell Science (Impact Factor: 5.33). 05/2012; 125(Pt 16):3790-800. DOI: 10.1242/jcs.101048
Source: PubMed

ABSTRACT Multinucleated muscle fibres arise by fusion of precursor cells called myoblasts. We previously showed that CKIP-1 ectopic expression in C2C12 myoblasts increased cell fusion. In this work, we report that CKIP-1 depletion drastically impairs C2C12 myoblast fusion in vitro and in vivo during zebrafish muscle development. Within developing fast-twich myotome, Ckip-1 localises at the periphery of fast precursor cells, closed to the plasma membrane. Unlike wild-type myoblasts that form spatially arrayed multinucleated fast myofibres, Ckip-1-deficient myoblasts show a drastic reduction in fusion capacity. A search for CKIP-1 binding partners identified the ARPC1 subunit of Arp2/3 actin nucleation complex essential for myoblast fusion. We demonstrate that CKIP-1, through binding to plasma membrane phosphoinositides via its PH domain, regulates cell morphology and lamellipodia formation by recruiting the Arp2/3 complex at the plasma membrane. These results establish CKIP-1 as a regulator of cortical actin that recruits the Arp2/3 complex at the plasma membrane essential for muscle precursor elongation and fusion.

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