Mending Fences: Na,K-ATPase signaling via Ca 2+ in the maintenance of epithelium integrity.

Aperia A, Brismar H, Uhlén P

Cell Calcium 88 (-) 102210 [2020-04-26; online 2020-04-26]

Na,K-ATPase is a ubiquitous multifunctional protein that acts both as an ion pump and as a signal transducer. The signaling function is activated by ouabain in non-toxic concentrations. In epithelial cells the ouabain-bound Na,K-ATPase connects with the inositol 1,4,5-trisphosphate receptor via a short linear motif to activate low frequency Ca2+ oscillations. Within a couple of minutes this ouabain mediated signal has resulted in phosphorylation or dephosphorylation of 2580 phospho-sites. Proteins that control cell proliferation and cell adhesion and calmodulin regulated proteins are enriched among the ouabain phosphor-regulated proteins. The inositol 1,4,5-trisphosphate receptor and the stromal interaction molecule, which are both essential for the initiation of Ca2+ oscillations, belong to the ouabain phosphor-regulated proteins. Downstream effects of the ouabain-evoked Ca2+ signal in epithelial cells include interference with the intrinsic mitochondrial apoptotic process and stimulation of embryonic growth processes. The dual function of Na,K-ATPase as an ion pump and a signal transducer is now well established and evaluation of the physiological and pathophysiological consequences of this universal signal emerges as an urgent topic for future studies.

Integrated Microscopy Technologies Stockholm [Collaborative]

QC bibliography QC xrefs

PubMed 32380435

DOI 10.1016/j.ceca.2020.102210

Crossref 10.1016/j.ceca.2020.102210

pii: S0143-4160(20)30052-X