Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca 2+-ATPases and Key Regulators of Ca 2+ Clearance

Neuron. 2017 Nov 15;96(4):827-838.e9. doi: 10.1016/j.neuron.2017.09.038. Epub 2017 Oct 19.

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 to be key regulators of Ca2+ 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 Ca2+ transport, as well as submembraneous Ca2+ concentrations under steady-state conditions. Together, these results establish neuroplastin and basigin as obligatory auxiliary subunits of native PMCAs and key regulators of intracellular Ca2+ concentration.

Keywords: Basigin; Ca2+ Clearance; Ca2+-ATPase; Ca2+-Signalling; Neuroplastin; PMCA; plasma membrane targeting; transporter.

MeSH terms

  • Animals
  • Basigin / metabolism*
  • Calcium / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Female
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Plasma Membrane Calcium-Transporting ATPases / metabolism*
  • Protein Subunits / metabolism

Substances

  • Membrane Glycoproteins
  • Protein Subunits
  • neuroplastin protein, mouse
  • Basigin
  • Plasma Membrane Calcium-Transporting ATPases
  • Calcium