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