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.
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ABSTRACT: Vertebrate skeletal muscle is composed of distinct types of fibre that are functionally adapted through differences in their physiological and metabolic properties. An understanding of the molecular basis of fibre-type specification is of relevance to human health and fitness. The zebrafish provides an attractive model for investigating fibre type specification; not only are their rapidly developing embryos optically transparent, but in contrast to amniotes, the embryonic myotome shows a discrete temporal and spatial separation of fibre type ontogeny that simplifies its analysis. Here we review the current state of understanding of muscle fibre type specification and differentiation during embryonic development of the zebrafish, with a particular focus on the roles of the Prdm1a and Sox6 transcription factors, and consider the relevance of these findings to higher vertebrate muscle biology.Mechanisms of development 06/2013; · 2.83 Impact Factor