Local control of signaling in heart includes a balance of kinase and phosphatase activities that regulate the cardiac cell function. In fact such segregated signaling regulates transverse-tubule cytoskeletal architecture of the cardiac myocyte. These new findings have broad impact since dysfunction of excitation-contraction (EC) coupling and mis-localization of cytoskeletal proteins have been linked to acquired and inherited dilated cardiomyopathies in humans and animal models.
The specific goals of Project 1 are integrated with the efforts of colleagues on this PPG and explore how Ca2+ signaling depends upon dynamic cytoskeletal organization and how they are both regulated by local, targeted signaling cascades in heart. This project seeks to explore this core hypothesis by critically examining the role of targeted signaling of the PP2A family of serine/threonine protein phosphatases in cardiac myocytes.