Stop making waves: A new regulatory role for cardiac myosin binding protein-C in contraction скачать в хорошем качестве

Stop making waves: A new regulatory role for cardiac myosin binding protein-C in contraction

Samantha Harris, Ph.D. Professor Cellular and Molecular Medicine University of Arizona Cardiac myosin binding protein-C (cMyBP-C) is a critical regulator of heart muscle contraction that is phosphorylated by adrenergic stimuli (“fight-or-flight” responses), whereas mutations in MYBPC3, the gene encoding cMyBP-C, are the most frequent cause of hypertrophic cardiomyopathy (HCM). However, the mechanisms by which cMyBP-C affects cardiac contraction are complex and only partly understood. A primary obstacle has been the lack of methods to rapidly modify cMyBP-C at its position in sarcomeres in situ. To overcome this obstacle, we designed a novel hybrid genetic/protein engineering approach to efficiently “cut and paste” cMyBP-C at its native location in sarcomeres. Results using this new method showed that loss of cMyBP-C (“cut”) caused sustained auto-oscillatory contractions when detergent permeabilized myocytes were activated by submaximal [Ca2+]. Ligation (“paste”) of new recombinant cMyBP-C abolished the oscillations, but phosphorylated cMyBP-C did not. These results suggest a previously unrecognized role of cMyBP-C in damping sarcomere-generated contractile waves in a phosphorylation dependent manner. This Pioneers in Biomedical Research Seminar is presented by the Fralin Biomedical Research Institute and co-sponsored by the institute's Center for Heart and Reparative Medicine Research.