Transition of Homer isoforms during skeletal muscle regeneration

Homer represents a new and diversified family of proteins that includes several isoforms, Homer 1, 2, and 3; some of these isoforms have been reported to be present in striated muscles. In this study, the presence of Homer isoforms 1a, 1b/c/d, 2b, and 3 was thoroughly investigated in rat skeletal muscles under resting conditions. Transition in Homer isoforms compositon was studied under experimental conditions of short-term and long-term adaptation, e.g., fatigue and regeneration, respectively. First, we show that Homer 1a was constitutively expressed and was transiently upregulated during regeneration. In C₂C₁₂ cell cultures, Homer 1a was also upregulated during formation of myotubes. No change of Homer 1a was observed in fatigue. Second, Homer 1b/c/d and Homer 2b were positively and linearly related to muscle mass change during regeneration, and third, Homer 3 was not detectable under resting conditions but was transiently expressed during regeneration although with a temporal pattern distinct from that of Homer 1a. Thus a switch in Homer isoforms is associated to muscle differentiation and regeneration. Homers may play a role not only in signal transduction of skeletal muscle, in particular regulation of Ca²⁺ release from sarcoplasmic reticulum (Ward CW, Feng W, Tu J, Pessah IN, Worley PF, and Schneider MF. Homer protein increases activation of Ca²⁺ sparks in permeabilized skeletal muscle. J Biol Chem 279: 5781–5787, 2004), but also in adaptation. fatigue; immediate early gene; muscle adaptation; myogenesis