The plasma membrane Ca2+-ATPase: Regulation by PSD-95/Dlg/Zo-1 scaffolds

Since its first characterization in the erythrocyte membrane the plasma membrane Ca2+-ATPase has been well-defined as a ubiquitous mechanism for the efflux of Ca2+ from eukaryotic cells. With 4 isoforms and potentially 30 splice variants, defining the absolute physiological role of plasma membrane Ca2+-ATPase has been difficult and very limited due to the lack of effective blockers/antibodies and difficulties in measuring the activity of individual isoforms. This review highlights recent developments showing that specific plasma membrane Ca2+-ATPase isoforms are subject to dynamic regulation by PSD-95/Dlg/Zo-1 scaffold proteins. Such interactions support a new paradigm, that by serving as key players in multifunctional protein complexes, transporters can regulate other signalling processes independent of their primary ion pumping function.