Obscurin and titin as interacting partners during cardiac differentiation and remodeling

Abstract

Obscurin is a recently identified giant muscle protein that binds titin, another giant muscle protein of the immunoglobulin superfamily. Both proteins, in addition to their structural domains, contain the kinase‐like domains that appear to be involved in signal transduction. Little is known about the structural relationship and the expression dynamics of these proteins during growth and adaptive reactions of cardiac muscle. The goal of this study was to comparatively investigate the localization patterns of these proteins during differentiation and remodeling of cardiac myocytes in vivo and in cell culture using high resolution confocal microscopy. We also performed the comparative analysis of obscurin and titin incorporation into nascent sarcomeres on the tips of growing myofibrils. We found that obscurin and titin incorporated into forming myofibrils relatively early, before the establishment of registered, aligned pattern of myofibril structure typical of the mature contractile system. Co‐localization of titin and obscurin at the level of the Z‐discs and their close topographical apposition at the A‐I band interfaces of sarcomeres indicate their structural interaction within these structures. The labeling patterns of obscurin and titin expression rapidly changed during structural remodeling of differentiated cardiomyocytes and appear to be one of the earliest detectable markers of this process. Interestingly, downregulation of both obscurin and titin resulted in similar changes in the structure of the contractile system of cardiac myocytes. These data suggest the synergistic involvement of these two proteins in the support of the structural integrity of the contractile apparatus in cardiac muscle. Supported by MDA3803 and NIH HL075093