Cell signaling Microdomain with Na,K-ATPase and inositol 1,4,5-trisphosphate receptor generates calcium oscillations
2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 50, 50355-50361 p.Article in journal (Refereed) Published
Recent studies indicate novel roles for the ubiquitous ion pump, Na,K-ATPase, in addition to its function as a key regulator of intracellular sodium and potassium concentration. We have previously demonstrated that ouabain, the endogenous ligand of Na, K-ATPase, can trigger intracellular Ca2+ oscillations, a versatile intracellular signal controlling a diverse range of cellular processes. Here we report that Na, K-ATPase and inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) form a cell signaling microdomain that, in the presence of ouabain, generates slow Ca2+ oscillations in renal cells. Using fluorescent resonance energy transfer ( FRET) measurements, we detected a close spatial proximity between Na, K-ATPase and InsP(3)R. Ouabain significantly enhanced FRET between Na, K-ATPase and InsP(3)R. The FRET effect and ouabain-induced Ca2+ oscillations were not observed following disruption of the actin cytoskeleton. Partial truncation of the NH2 terminus of Na, K-ATPase catalytic alpha1-subunit abolished Ca2+ oscillations and downstream activation of NF-kappaB. Ouabain-induced Ca2+ oscillations occurred in cells expressing an InsP3 sponge and were hence independent of InsP3 generation. Thus, we present a novel principle for a cell signaling microdomain where an ion pump serves as a receptor.
Place, publisher, year, edition, pages
2003. Vol. 278, no 50, 50355-50361 p.
protein-kinase-c, 2-aminoethoxydiphenyl borate 2-apb, alpha-subunit, na+/k+-atpase, ca2+ release, gene-expression, ouabain, identification, channels, plasma
IdentifiersURN: urn:nbn:se:kth:diva-23010DOI: 10.1074/jb.M305378200ISI: 000187068200085OAI: oai:DiVA.org:kth-23010DiVA: diva2:341708
QC 201005252010-08-102010-08-10Bibliographically approved