The sarcomere and the nucleus: functional links to hypertrophy, atrophy and sarcopenia

Skeletal muscle has a remarkable ability to rapidly adjust to changes in physiological requirements. This includes hypertrophic muscle growth and the atrophic loss of muscle mass, both of which occur in response to hormonal, endocrine and mechanical stimuli. In ageing muscle, sarcopenia (the loss of muscle fibres) can aggravate hormonally and mechanically induced atrophy. Hypertrophy and atrophy are associated with changes in sarcomeric protein composition and metabolic enzymes. The coordinated changes of transcriptional and splice mechanisms, protein turnover and cell fate integrates signalling pathways from hormone and cytokine receptors, as well as the sarcomere itself. This involves a number of proteins that shuttle between sarcomeric and nonsarcomeric localisations and thus convey signals from the contractile machinery to the nucleus. The M-band is emerging as a hub mainly for protein-kinase regulated ubiquitin signalling and protein turnover, whereas the I-band and Z-disk contain stretch-sensitive pathways involving transcriptional modifiers. Disruptions of these pathways can cause hereditary myopathies.