Loss of mouse cardiomyocyte talin-1 and talin-2 leads to β-1 integrin reduction, costameric instability, and dilated cardiomyopathy

• DOI: 10.1073/pnas.1701416114
• Publication Date: 2017-07-12T01:10:19Z
• Authors: Ana Maria Manso; Hideshi Okada; Francesca M. Saka...; Emily Moreno; Susan J. Monkley; Ruixia Li; David R. Critchley; Robert S. Ross
• Keywords: Cardiomyopathy, Dilated; Talin; 0301 basic medicine; 570; Cardiomyopathy; Medical Physiology; 610; heart; Cardiovascular; Mice; 03 medical and health sciences; Rare Diseases; Dilated; 2.1 Biological and endogenous factors; Animals; Myocytes, Cardiac; Myocytes; Biomedical and Clinical Sciences; costameres; talin; Integrin beta1; Myocardium; Biological Sciences; 3. Good health; Heart Disease; integrins; Biochemistry and Cell Biology; Cardiac; cardiomyopathy

Significance Heart failure is a significant health problem with a poorly understood molecular basis. Continuous contraction–relaxation cycles of the heart and its cardiomyocytes (CMs) require strong interactions between intracellular proteins and the surrounding extracellular matrix to maintain normal heart function. We exhaustively studied the function of the cytoskeletal protein talin (Tln), and its two isoforms, Tln1 and Tln2, in CMs and the intact heart. Both Tln isoforms can independently support costamere, CM, and whole-heart function. Yet, combined deletion of CM Tln1 and Tln2 destabilized the myocardium, leading to heart failure. This study significantly advances knowledge about the basic biology of talin, particularly given its study in vivo, and advances understanding of Tln’s role in maintenance of normal heart muscle function.