Interactome of splice variants of the ß2-subunit of L-type voltage-gated calcium channels in cardiac myocytes.

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The compartmentalization of calcium influxes through L-type voltage-gated calcium channels (LTCCs) in cardiomyocytes is necessary for the correct regulation of cardiac processes. LTCCs are located in different subcellular compartments in the sarcolemma. Cavß is the most important LTCCs regulatory subunit. Of the four Cavß isoforms, Cavß2 is predominantly expressed in cardiomyocytes. Our recent data and previous reports have detected different Cavß2 splice variants coexisting in adult mouse and human cardiomyocytes. In addition, the association of this subunit to diverse proteins besides the LTCCs has also been reported. Our preliminary results show that diverse subpopulations of Cavß2 are located in different subcellular microdomains of the sarcolemma in mouse cardiomyocytes. These different subpopulations could correspond to specific splice variants being involved in the recruitment of members of distinctive signaling pathways to LTCCs vicinity. Therefore, this project has two main goals. First, we will focus on the identification of proteins interacting with each Cavß2 splice variant expressed in mouse cardiomyocytes. Secondly, we will study the cellular localization and protein expression of each Cavß2 splice variant and their associated proteins under physiological and cardiac hypertrophy conditions. To reach these objectives we will combine tandem affinity purifications, mass spectrometry, systems biology analyses and super-resolution microscopy.