PMID- 29874125
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 32
IP  - 12
DP  - 2018 Jun 6
TI  - Structure before function: myosin binding protein-C slow is a structural protein 
      with regulatory properties.
PG  - fj201800624R
LID - 10.1096/fj.201800624R [doi]
AB  - 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  approximately 50% for slow and fast myosin to  approximately 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.
FAU - Geist, Janelle
AU  - Geist J
AD  - Department of Biochemistry and Molecular Biology, University of Maryland School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Ward, Christopher W
AU  - Ward CW
AD  - Department of Orthopedics, University of Maryland School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Kontrogianni-Konstantopoulos, Aikaterini
AU  - Kontrogianni-Konstantopoulos A
AD  - Department of Biochemistry and Molecular Biology, University of Maryland School 
      of Medicine, Baltimore, Maryland, USA.
LA  - eng
GR  - R01 AR071614/AR/NIAMS NIH HHS/United States
GR  - R01 AR071618/AR/NIAMS NIH HHS/United States
GR  - T32 AR007592/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20180606
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
PMC - PMC6219831
OTO - NOTNLM
OT  - CRISPR
OT  - contractility kinetics
OT  - force production
OT  - in vivo gene-transfer
OT  - thick filament
COIS- This work was supported by the Training Program in Muscle Biology Grant T32 
      AR007592-17 (to J.G.); U.S. National Institutes of Health, National Institute of 
      Arthritis and Musculoskeletal and Skin Diseases Grant R01 AR071618 (to C.W.W.); 
      and Muscular Dystrophy Association Research Grant 313579 (to A.K.-K). The authors 
      thank Dr. Ramzi Khairallah (Myologica LLC, Baltimore, MD, USA) for collaborative 
      assistance with the development of the in vivo FDB assay. The authors declare no 
      conflicts of interest.
EDAT- 2018/06/07 06:00
MHDA- 2018/06/07 06:00
PMCR- 2019/12/01
CRDT- 2018/06/07 06:00
PHST- 2018/06/07 06:00 [pubmed]
PHST- 2018/06/07 06:00 [medline]
PHST- 2018/06/07 06:00 [entrez]
PHST- 2019/12/01 00:00 [pmc-release]
AID - FJ_201800624R [pii]
AID - 10.1096/fj.201800624R [doi]
PST - aheadofprint
SO  - FASEB J. 2018 Jun 6;32(12):fj201800624R. doi: 10.1096/fj.201800624R.