Palmiter K A, Kitada Y, Muthuchamy M, Wieczorek D F, Solaro R J
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago, 60612, USA.
J Biol Chem. 1996 May 17;271(20):11611-4. doi: 10.1074/jbc.271.20.11611.
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.
尽管原肌球蛋白（Tm）同工型转换作为横纹肌功能状态的关键决定因素具有潜在作用，但在完整晶格中，其对哺乳动物肌丝激活和调节的影响仍不清楚。通过转基因方法在小鼠心脏中特异性地将β-Tm替换为天然α-Tm，我们得以揭示心脏中Tm同工型转换的新功能。含有β-Tm的肌丝表现出以下特征：通过紧密结合的横桥增强细肌丝的激活，稳态力的Ca2+敏感性增加，以及由cAMP依赖性磷酸化诱导的Ca2+ - 力关系向右移位减少。我们的结果首次证明了Tm同工型转换对完整晶格中哺乳动物细肌丝激活的特定影响，并表明Tm在通过肌钙蛋白磷酸化调节肌丝活性方面具有重要作用。
