Normal cell function relies on proteins working properly at the right place, at the right time and at the right amount. The “Calcium Channel Biology” research group aims at understanding the regulation and cellular impact of ionic and non-ionic functions of voltage-activated calcium channels along the intracellular life cycle of the channel protein; from their synthesis in the endoplasmic reticulum, along their transport to their site of function and during their lifespan at the plasma membrane to their removal.
The multisubunit voltage-activated calcium channel opens in response to changes in the voltage across the membrane of excitable cells, allowing the entry of calcium, the ubiquitous intracellular messenger that regulates almost all aspects of cell function. The channel complex and its subunits also exhibit non-ionic functions that regulate cellular processes independent of ion permeation.
Our research seeks to elucidate the determinants underlying the functional plasticity and availability of these multi-tasking proteins, the role of post-translational modifications, and protein-protein interactions that reroute the subunits to different cellular pathways, and the mechanisms responsible for monitoring and clearing defective subunits. We also explore deregulation of these functions in cardiac and neurological disorders caused by genetic mutations in calcium channel subunits. We focus on the function of the Cavβ subunit on cardiac muscle cells in health and disease, using primary cultures from knock-out mice and human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes.
To address these questions, we use a multidisciplinary approach combining molecular biology, protein biochemistry, proteomics and interactome analysis, gene-based downregulation, electrophysiology, and laser scanning and spinning disk microscopy to image calcium channels in living cells.
