Exchange of beta- for alpha-tropomyosin in hearts of transgenic mice induces changes in thin filament response to Ca2+, strong cross-bridge binding, and protein phosphorylation.
Despite its potential as a key determinant of the functional state of striated muscle, the impact of tropomyosin (Tm) isoform switching on mammalian myofilament activation and regulation in the intact lattice remains unclear. Using a transgenic approach to specifically exchange beta-Tm for the native alpha-Tm in mouse hearts, we have been able to uncover novel functions of Tm isoform switching in the heart. The myofilaments containing beta-Tm demonstrated an increase in the activation of the thin filament by strongly bound cross-bridges, an increase in Ca2+ sensitivity of steady state force, and a decrease in the rightward shift of the Ca2+-force relation induced by cAMP-dependent phosphorylation. Our results are the first to demonstrate the specific effects of Tm isoform switching on mammalian thin filament activation in the intact lattice and suggest an important role for Tm in modulation of myofilament activity by phosphorylation of troponin.
Palmiter
K A
KA
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago, 60612, USA.
Kitada
Y
Y
Muthuchamy
M
M
Wieczorek
D F
DF
Solaro
R J
RJ
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D014335:Tropomyosin / Q000502:physiology*
D011506:Proteins; D014335:Tropomyosin; D002118:Calcium