University of Freiburg
Host: Jian Yang
Title: Native PMCAs – Proteomic surprises with old Ca2+ pumps
Abstract: Plasma membrane Ca2+-ATPases (PMCAs), a family of P-type ATPases, extrude Ca2+ ions from the cytosol to the extracellular space and are considered key regulators of Ca2+-signaling. Molecularly, these classical pumps have been considered as monomers very similar to their counterparts in the sarcoplasmic reticulum (SERCA).
I will show that the ‘functional proteomics’ approach established over the last decade uncovered native PMCAs as heteromeric complexes that are assembled from two pore-forming PMCA1-4 subunits and two of the single-span membrane proteins either neuroplastin or basigin. Contribution of the two Ig-domain containing proteins varies among different types of cells and along postnatal development. Complex formation of neuroplastin/basigin with PMCAs1-4 occurs in the endoplasmic reticulum and is obligatory for stability of the PMCA proteins and for delivery of PMCA complexes to the surface membrane. Knockout and (over)-expression of both neuroplastin and basigin profoundly affect the time-course of PMCA-mediated Ca2+ transport, as well as submembraneous Ca2+ concentrations under steady-state conditions.
These results establish neuroplastin and basigin as obligatory auxiliary subunits of native PMCAs and key regulators of intracellular Ca2+ concentration.