A2 - Molecular and Cellular aspects of tissue adaptation and repair: A symposium in honour of Professor Geoffrey Goldspink on the occasion of his retirement
نویسندگان
چکیده
Muscle growth requires a population(s) of myogenic progenitor cells (MPCs) or myoblasts that remain capable of proliferation and are regulated by signaling pathways responsive to both nutritional status and environmental conditions. Myotube formation involves the recognition and adhesion of myoblasts, the breakdown of muscle membranes and the remodeling of the actin cytoskeleton. Myotube production in fast myotomal muscle typically continues until ~40% of the maximum adult body length, and subsequent growth only involves fibre hypertrophy. Microarray experiments will be described to identify genes associated with the transition from hyperplastic to hypertrophic growth phenotypes in zebrafish. Insulin-like growth factor I (IGF-I) together with associated binding proteins and receptors plays a key role in regulating myogenesis and muscle fibre hypertrophy. The signals that regulate atrophy and hypertrophy are linked through the PI3K/AKT/mTOR pathway. Activation of the PI3k/ AKT/mTOR pathway by IGF-I activates a phosphorylation cascade that leads to an increase in translation and protein synthesis, resulting in fibre hypertrophy. Phosphorylation of Akt also inhibits regulators of fibre atrophy such as the muscle specific ubiquitin ligases MAFbx and MuRF1, through phosphorylation of FOXO transcription factors. The myotomal muscles act as a reservoir of amino acids during seasonal fasting and for the elaboration of gonads prior to reproduction. The use of fasting-refeeding paradigms to challenge the genetic pathways regulating muscle fibre hypertrophy in Atlantic salmon will be described. In vitro cell culture systems have also been developed which enable manipulative experiments and analysis of the function of individual genes. Supported by BBSRC. Email Address for correspondence: [email protected]
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