Loss of SM-B myosin affects muscle shortening velocity and maximal force development.
We used an exon-specific gene-targeting strategy to generate a mouse model deficient only in the SM-B myosin isoform. Here we show that deletion of exon-5B (specific for SM-B) in the gene for the heavy chain of smooth muscle myosin results in a complete loss of SM-B myosin and switching of splicing to the SM-A isoform, without affecting SM1 and SM2 myosin content. Loss of SM-B myosin does not affect survival or cause any overt smooth muscle pathology. Physiological analysis reveals that absence of SM-B myosin results in a significant decrease in maximal force generation and velocity of shortening in smooth muscle tissues. This is the first in vivo study to demonstrate a functional role for the SM-B myosin isoform. We conclude that the extra seven-residue insert in the surface loop 1 of SM-B myosin is a critical determinant of crossbridge cycling and velocity of shortening.
Babu
G J
GJ
Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210, USA.
Loukianov
E
E
Loukianova
T
T
Pyne
G J
GJ
Huke
S
S
Osol
G
G
Low
R B
RB
Paul
R J
RJ
Periasamy
M
M
D000818:Animals; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012326:RNA Splicing; D024745:Smooth Muscle Myosins / Q000235:genetics / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism
D020033:Protein Isoforms; D024745:Smooth Muscle Myosins