Compartmentation of protein synthesis, mRNA targeting and c-myc expression during muscle hypertrophy and growth

Summary

Introduction

Post-natal muscle growth, which is one of the major growth processes of the mammalian body, involves a combination of myofibre elongation and an increase in fibre diameter. The latter occurs by hypertrophy (increase in size without cell division) whilst muscle elongation is achieved by addition of extra cell units. Muscle mass also increases in response to workload, to stretch and to anabolic agents, and in all cases the predominant myotrophic response involves hypertrophy. This requires increased synthesis of myofibrillar protein and a rapid growth and assembly of the contractile myofibrils whilst structural integrity and physiological function of the sarcomeres is maintained. During muscle hypertrophy the increased amounts of newly synthesized protein must be targeted to specific parts of the fibre to ensure that a spatially precise myofibrillar assembly can occur.

All cells target proteins to specific intracellular sites but the organization of the synthesis of the myofibrillar proteins, particularly large proteins such as titin and myosin, presents the long and ordered myofibre with unique logistic problems. These problems of cell organization occur during normal turnover of the myofibrillar proteins and myofibril repair, both of which require the newly synthesized proteins to be incorporated into the contractile apparatus, but are exacerbated during hypertrophy. Thus the intracellular targeting of newly synthesized protein is crucial to ordered muscle hypertrophy and to maintenance of the myofibrillar structure. As illustrated in Fig. 1, this targeting could theoretically be achieved by targeting of the synthesized protein, by spatial organization of ribosomes and mRNAs so that synthesis occurs close to the protein's site of function or by co-translational assembly.