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

Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+-ATPases and Key Regulators of Ca2+ Clearance.

Author information

1
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
2
Carl-Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, Liebigstr. 27, 04103 Leipzig, Germany.
3
Department of Dermatology, Venerology and Allergology, Medical Faculty of University of Leipzig, Max-Bürger-Forschungszentrum, Johannisallee 30, 04103 Leipzig, Germany.
4
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Center for Biological Signaling Studies (BIOSS), Schänzlestrasse 18, 79104 Freiburg, Germany.
5
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Center for Biological Signaling Studies (BIOSS), Schänzlestrasse 18, 79104 Freiburg, Germany. Electronic address: bernd.fakler@physiologie.uni-freiburg.de.
6
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Logopharm GmbH, Schlossstrasse 14, 79232 March-Buchheim, Germany; Center for Biological Signaling Studies (BIOSS), Schänzlestrasse 18, 79104 Freiburg, Germany. Electronic address: uwe.schulte@physiologie.uni-freiburg.de.

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

PMID:
29056295
DOI:
10.1016/j.neuron.2017.09.038
[Indexed for MEDLINE]
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