First Author | Schmidt N | Year | 2017 |
Journal | Neuron | Volume | 96 |
Issue | 4 | Pages | 827-838.e9 |
PubMed ID | 29056295 | Mgi Jnum | J:256134 |
Mgi Id | MGI:6114338 | Doi | 10.1016/j.neuron.2017.09.038 |
Citation | Schmidt N, et al. (2017) Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca(2+)-ATPases and Key Regulators of Ca(2+) Clearance. Neuron 96(4):827-838.e9 |
abstractText | Plasma membrane Ca(2+)-ATPases (PMCAs), a family of P-type ATPases, extrude Ca(2+) ions from the cytosol to the extracellular space and are considered to be key regulators of Ca(2+) signaling. Here we show by functional proteomics that native PMCAs are 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 or 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 Ca(2+) transport, as well as submembraneous Ca(2+) concentrations under steady-state conditions. Together, these results establish neuroplastin and basigin as obligatory auxiliary subunits of native PMCAs and key regulators of intracellular Ca(2+) concentration. |