Introducing a series of topical special issues of the Journal of Muscle Research and Cell Motility

Abstract

The Journal of Muscle Research aims to serve its readers not only by publishing original studies in muscle and motility structure and function but also by informing readers of the state of the art in muscle research and cell motility and to promote debate. This issue of the Journal of Muscle Research and Cell Motility is the first of a series of topical special issues that combine original research with review articles related to a specific subject that we plan to publish once or twice a year. Further topical issues are being planned and we would welcome ideas for the themes to be covered in future issues. In this issue, articles are devoted to cardiac myosinbinding protein-C. When C-protein, or myosin-binding protein-C (MyBP-C) was discovered in skeletal muscle in the early 1970s by Gerald Offer (Offer 1972; Offer et al. 1973), MyBP-C was thought to be merely a structural protein component of the thick filament. Interest in the functions of MyBP-C were galvanised when it was found that the cardiac isoform, encoded by the MYBPC3 gene on chromosome 11, was mutated in cases of hereditary hypertrophic cardiomyopathy (HCM) (Bonne et al. 1995; Watkins et al. 1995). By now, mutations in MYBPC3 are the second-most frequently identified mutations that cause HCM (Schlossarek et al. 2011), with carriers of a specific pathogenic mutation amounting up to 4 % of the population of Indian descent (Dhandapany et al. 2009). It has become clear that MyBP-C must play important roles in both the regulation of contractility and as the assembly of muscle myofibrils. MyBP-C is transcribed from three related genes (MYBPC1-3), which encode the slow, fast and cardiac isoforms. Like many other myofibrilassociated structural proteins, MyBP-C is composed of a series of hundred-residue domains of the intracellular immunoglobulin and fibronectin families—10–11 in the case of MyBP-C (Furst and Gautel 1995; Otey et al. 2009). This molecular architecture is shared with the small MyBPC homologue, myosin-binding protein-H (Vaughan et al. 1993) and other myofibrillar proteins like myopalladin, myotilin, the myomesin isogenes and the giant scaffold and signalling proteins titin and obscurin (KontrogianniKonstantopoulos et al. 2009). Earlier work by the laboratories of Gerald Offer, Carl Moos, Roger Starr, Rick Moss, Polly Hofmann, Criss Hartzell and others had implicated MyBP-C in contraction regulation by interactions with actin or myosin filament components, possibly dynamically modulated by phosphorylation by cAMP and calcium/calmodulin dependent protein kinases in the case of the cardiac isoform (see articles in this issue for a review of the literature). The elucidation of the primary structure of both skeletal and cardiac MyBP-C isoforms pinpointed these phosphorylation sites to the N-terminal region within a sequence distinct from the immunoglobulin or fibronectin-like domains that form the remainder of the protein (Einheber and Fischman 1990; Furst et al. 1992; Gautel et al. 1995). This MyBP-C motif has since been implicated as the major domain involved in contraction regulation by interactions that have been localised to both the actin and myosin S. B. Marston NHLI, Myocardial Function, Imperial College London, Imperial Centre for Translational and Experimental Medicine, London W12 0NN, UK e-mail: S.marston@imperial.ac.uk