Plasma membrane Ca2+ ATPase isoform 4B binds to membrane-associated guanylate kinase (MAGUK) proteins via their PDZ (PSD-95/Dlg/ZO-1) domains

Eunjoon Kim, Steven J. DeMarco, Shirin M. Marfatia, Athar H. Chishti, Morgan Sheng, Emanuel E. Strehler

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Plasma membrane Ca2+ ATPases are P-type pumps important for intracellular Ca2+ homeostasis. The extreme C termini of alternatively spliced 'b'-type Ca2+ pump isoforms resemble those of K+ channels and Nmethyl-D-aspartate receptor subunits that interact with channel-clustering proteins of the membrane-associated guanylate kinase (MAGUK) family via PDZ domains. Yeast two-hybrid assays demonstrated strong interaction of Ca2+ pump 4b with the PDZ1+2 domains of several mammalian MAGUKs. Pump 4b and PSD- 95 could be co-immunoprecipitated from COS-7 cells overexpressing these proteins. Surface plasmon resonance revealed that a C-terminal pump 4b peptide interacted with the PDZ1+2 domains of hDlg with nanomolar affinity (K(D) = 1.6 nM), whereas binding to PDZ3 was in the micromolar range (K(D) = 1.2 μM). In contrast, the corresponding C-terminal peptide of Ca2+ pump 2b interacted weakly with PDZ1+2 and not at all with PDZ3 of hDlg. Ca2+ pump 4b bound strongly to PDZ1+2+3 of hDlg on filter assays, whereas isoform 2b bound weakly, and the splice variants 2a and 4a failed to bind. Together, these data demonstrate a direct physical binding of Ca2+ pump isoform 4b to MAGUKs via their PDZ domains and reveal a novel role of alternative splicing within the family of plasma membrane Ca2+ pumps. Alternative splicing may dictate their specific interaction with PDZ domain-containing proteins, potentially influencing their localization and incorporation into functional multiprotein complexes at the plasma membrane.

Original languageEnglish (US)
Pages (from-to)1591-1595
Number of pages5
JournalJournal of Biological Chemistry
Issue number3
StatePublished - Jan 16 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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