The fast muscle Myosin light chain mylpfa is essential for fast muscle function and integrity
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Date
2018-05
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The Ohio State University
Abstract
The structure and function of muscles are vital to human health and mobility. Muscle fibers contain contractile proteins organized into units called sarcomeres that are necessary for muscle function. Mutations in proteins of the sarcomere, such as in the Myosin regulatory light chains, can lead to degenerative diseases in humans, such as nemaline and cardiac myopathies. These Myosin regulatory light chain proteins regulate Myosin heavy chain protein to alter the kinetics of muscle contraction. I hypothesize that mylpfa is necessary not only for Myosin heavy chain regulation but also vital for sarcomere formation in fast muscle. To test this, we generated knockouts in four zebrafish Myosin light chain genes, mylpfa, mylpfb, myl1a, and myl1b. The mylpfa-/- mutants have severe defects in all fast muscle fibers, while sarcomeres in slow muscle fibers appear unaffected. Mutants for the second Mylpf in zebrafish, mylpfb-/-, appear normal, indicating that mylpfa is the more important of the two Mylpf homologs. Consistent with my hypothesis, mylpfa-/- mutant embryos have weakened muscles caused by severely disrupted sarcomere structure. Later, during larval stages, the weakened mylpfa-/- mutant muscle fibers degenerate, resulting in loss of fast muscle fibers. Thus, our findings reveal that in addition to their role in muscle contraction, Mylpf genes are vital to sarcomere formation and muscle fiber integrity in fast muscles. Further investigation into how mylpfa functions in sarcomere assembly and how sarcomere assembly influences fiber integrity may help explain degenerative muscle diseases caused by mutations in sarcomeric proteins.
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Keywords
Myosin light chain, Muscle development, CRISPR/Cas9, Zebrafish, Sarcomere