CKIP-1 regulates mammalian and zebrafish myoblast fusion

J Cell Sci. 2012 Aug 15;125(Pt 16):3790-800. doi: 10.1242/jcs.101048. Epub 2012 May 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Communication / physiology
  • Cell Differentiation / physiology
  • Cell Fusion
  • Cell Line
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mammals
  • Membrane Fusion / physiology*
  • Mice
  • Myoblasts / cytology*
  • Myoblasts / metabolism
  • Transfection
  • Zebrafish

Substances

  • Actin-Related Protein 2-3 Complex
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • PLEKHO1 protein, human