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Structure before function: myosin binding protein‐C slow is a structural protein with regulatory properties
Author(s) -
Geist Janelle,
Ward Christopher W.,
KontrogianniKonstantopoulos Aikaterini
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800624r
Subject(s) - geist , library science , chemistry , computer science , philosophy , epistemology
Myosin binding protein‐C slow (sMyBP‐C) comprises a family of accessory proteins in skeletal muscles that bind both myosin and actin filaments. Herein, we examined the role of sMyBP‐C in adult skeletal muscles using in vivo gene transfer and clustered regularly interspaced short palindromic repeats technology to knock down all known sMyBP‐C variants. Our findings, confirmed in two different skeletal muscles, demonstrated efficient knockdown (KD) of sMyBP‐C (>70%) resulting in notably decreased levels of thick, but not thin, filament proteins ranging from ~50% for slow and fast myosin to ~20% for myomesin. Consistent with this, A bands were selectively distorted, and sarcomere length was significantly reduced. Contrary to earlier in vitro studies showing that addition of recombinant sMyBP‐C slows down the formation of actomyosin crossbridges, our work demonstrates that KD of sMyBP‐C in intact myofibers results in decreased contraction and relaxation kinetics under no‐load conditions. Similarly, KD muscles develop markedly reduced twitch and tetanic force and contraction velocity. Taken together, our results show that sMyBP‐C is essential for the regular organization and maintenance of myosin filaments into A bands and that its structural role precedes its ability to regulate actomyosin crossbridges.—Geist, J., Ward, C. W., Kontrogianni‐Konstantopoulos, A. Structure before function: myosin binding protein‐C slow is a structural protein with regulatory properties. FASEB J. 32, 6385–6394 (2018). www.fasebj.org