The SLMAP/Striatin complex: An emerging regulator of normal and abnormal cardiac excitation-contraction coupling.

The excitation-contraction (E-C) module involves a harmonized correspondence between the sarcolemma and the sarcoplasmic reticulum. This is provided by membrane proteins, which primarily shape the caveolae, the T-tubule/Sarcoplasmic reticulum (TT/SR) junction, and the intercalated discs (ICDs). Distortion of either one of these structures impairs myocardial contraction, and subsequently translates into cardiac failure. Thus, detailed studies on the molecular cues of the E-C module are becoming increasingly necessary to pharmacologically eradicate cardiac failure Herein we reviewed the organization of caveolae, TT/SR junctions, and the ICDs in the heart, with special attention to the Sarcolemma Membrane Associated Protein (SLMAP) and striatin (STRN) in cardiac membranes biology and cardiomyocyte contraction. We emphasized on their in vivo and in vitro signaling in cardiac function/dysfunction. SLMAP is a cardiac membrane protein that plays an important role in E-C coupling and the adrenergic response of the heart. Similarly, STRN is a dynamic protein that is also involved in cardiac E-C coupling and ICD-related cardiomyopathies. Both SLMAP and STRN are linked to cardiac conditions, including heart failure, and their role in cardiomyocyte function was elucidated in our laboratory. They interact together in a protein complex that holds therapeutic potentials for cardiac dysfunction. This review is the first of its kind to conceptualize the role of the SLMAP/STRN complex in cardiac function and failure. It provides in depth information on the signaling of these two proteins and projects their interaction as a novel therapeutic target for cardiac failure.