Plasma Membrane Ca2+-ATPase Isoforms 2b and 4b Interact Promiscuously and Selectively with Members of the Membrane-associated Guanylate Kinase Family of PDZ (PSD95/Dlg/ZO-1) Domain-containing Proteins

Steven J. DeMarco, Emanuel E. Strehler

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

Spatial and temporal regulation of intracellular Ca2+ signaling depends on localized Ca2+ microdomains containing the requisite molecular components for Ca2+ influx, efflux, and signal transmission. Plasma membrane Ca2+-ATPase (PMCA) isoforms of the "b" splice type contain predicted PDZ (PSD95/Dlg/ZO-1) interaction domains. The COOH-terminal tail of PMCA2b isolated the membrane-associated guanylate kinase (MAGUK) protein SAP97/hDlg as a binding partner in a yeast two-hybrid screen. The related MAGUKs SAP90/PSD95, PSD93/chapsyn-110, SAP97, and SAP102 all bound to the COOH-terminal tail of PMCA4b, whereas only the first three bound to the tail of PMCA2b. Coimmunoprecipitations confirmed the interaction selectivity between PMCA4b and SAP102 as opposed to the promiscuity of PMCA2b and 4b in interacting with other SAPs. Confocal immunofluorescence microscopy revealed the exclusive presence and colocalization of PMCA4b and SAP97 in the basolateral membrane of polarized Madin-Darby canine kidney epithelial cells. In hippocampal neurons, PMCA2b was abundant throughout the somatodendritic compartment and often extended into the neck and head of individual spines where it colocalized with SAP90/PSD95. These data show that PMCA "b" splice forms interact promiscuously but also with specificity with different members of the PSD95 family of SAPs. PMCA-SAP interactions may play a role in the recruitment and maintenance of the PMCA at specific membrane domains involved in local Ca2+ regulation.

Original languageEnglish (US)
Pages (from-to)21594-21600
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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