Date of Award
Doctor of Philosophy (PhD)
The goal of my dissertation was to compare and contrast the function of all three major isoforms of Myosin Binding Protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C, and cMyBP-C, respectively), with a focus on the least characterized isoform, fsMyBP-C. Using a variety of ex vivo, in vitro, and in silico methods, my research demonstrated that the N-terminal region of all MyBP-C isoforms bind to actin and shift tropomyosin, thus activating the thin filament during contraction. Furthermore, each isoform differentially activated the thin filament over isoform-specific ranges of Ca2+: slow-skeletal activates at low Ca2+, fast-skeletal activates at higher Ca2+, and cardiac activates over the full spectrum of Ca2+. I propose that different expression of MyBP-C isoforms allow striated muscles to fine tune its function. For example, the cardiac muscle sees the full range of Ca2+ on a beat-to-beat basis, and therefore cMyBP-C needs to operate over the full spectrum of Ca2+ with much higher frequency. Conversely, various skeletal muscles have vastly different roles: the demands of postural muscles are different than that of phasic muscles; thus, varied expression of slow-skeletal and fast-skeletal MyBP-C can ideally regulate the function of different muscles.
Lin, Brian Leei, "Heart and Sole: The Functional Role of Fast-Skeletal Myosin Binding Protein-C in Cardiac and Skeletal Muscle" (2016). Dissertations. 1952.
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Copyright © 2016 Brian Leei Lin