Myoregulatory protein

Myoregulatory proteins are a family of small, single-pass transmembrane micropeptides that play a critical role in regulating calcium homeostasis within muscle cells (Anderson et al., 2015, Cell). This family includes well-known members such as phospholamban (PLN) and sarcolipin (SLN), as well as more recently identified peptides like myoregulin (MLN), endoregulin (ELN), and dwarf open reading frame (DWORF) (Makarewich, 2020, Trends in Cell Biology). These proteins primarily function by interacting with the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump, either inhibiting or activating its ability to transport calcium ions from the cytosol into the sarcoplasmic reticulum (Nelson et al., 2016, Science). By modulating SERCA activity, myoregulatory proteins fine-tune the kinetics of muscle relaxation and contraction. Dysregulation or mutations in these proteins are linked to various pathologies, including heart failure and muscular dystrophies, making them attractive targets for therapeutic intervention (Goonasekera et al., 2021, Frontiers in Physiology). Current drug development strategies focus on small molecules or gene therapies designed to disrupt inhibitory interactions or restore healthy calcium cycling in diseased tissues (Trivieri et al., 2020, JACC: Basic to Translational Science).

Other names

MyoregulinPhospholambanSarcolipinDwarf open reading frameEndoregulinAnother-regulinSERCA-regulatory micropeptideRegulin

Modulation of the Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase (SERCA) pump activity to regulate calcium sequestration into the sarcoplasmic reticulum (Makarewich, 2020, Trends in Cell Biology).