title: CKIP-1 regulates mammalian and zebrafish myoblast fusion.
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.
authors.affiliation: 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.
authors.forename: Dominique
authors.initials: D
authors.lastname: Baas
authors.forename: Sabine
authors.initials: S
authors.lastname: Caussanel-Boude
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guiraud
authors.forename: Frederico
authors.initials: F
authors.lastname: Calhabeu
authors.forename: Emilie
authors.initials: E
authors.lastname: Delaune
authors.forename: Fanny
authors.initials: F
authors.lastname: Pilot
authors.forename: Emilie
authors.initials: E
authors.lastname: Chopin
authors.forename: Irma
authors.initials: I
authors.lastname: Machuca-Gayet
authors.forename: Aurélia
authors.initials: A
authors.lastname: Vernay
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bertrand
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rual
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Laurent
authors.initials: L
authors.lastname: Schaeffer
authors.forename: Evelyne
authors.initials: E
authors.lastname: Goillot
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D015027:Zebrafish
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human