Immune cell calcium signaling: how PMCAs shape Ca2+ levels for development and function of lymphocytes and dendritic cells

Calcium ions (Ca²⁺) are a universal signaling mediator that all cells use to translate receptor activation into distinct outcomes, but how immune cells terminate Ca²⁺ signaling is not completely understood. Here, we investigate the functions of a calcium ion (Ca²⁺) transporter family of plasma membrane Ca²⁺ ATPases (PMCAs). PMCA transports Ca²⁺ out of the cytosol to the extracellular milieu in response to rising Ca²⁺ levels activated by surface receptors. In humans, PMCAs are involved in many diseases including malaria, deafness, and high blood pressure, among others. We found that PMCA1 binds constitutively to a chaperone-like molecule called Neuroplastin in T and B cells and is responsible for terminating TCR- and BCR-induced Ca²⁺ signals. Based on these findings, we are currently studying the roles of PMCAs in lymphocyte, dendritic cell (DCs) and macrophage development and immune responses.