Phospholipase C-γ binds directly to the Na+/H+ exchanger 3 and is required for calcium regulation of exchange activity

Nicholas C. Zachos, Damian B. van Rossum, Xuhang Li, Gabriela Caraveo, Rafiquel Sarker, Boyoung Cha, Sachin Mohan, Stephen Desiderio, Randen L. Patterson, Mark Donowitz

Research output: Contribution to journalArticle

Abstract

Multiple studies suggest that phospholipase C-γ(PLC-γ) contributes to regulation of sodium/hydrogen exchanger 3 (NHE3) in the small intestine, although the mechanism(s) for this regulation remain unknown. We demonstrate here that PLC-γ binds directly to the C terminus of NHE3 and exists in similar sized multiprotein complexes as NHE3. This binding is dynamic and decreases with elevated [Ca2+]i. The PLC-γ-binding site in NHE3 was identified (amino acids 586-605) and shown to be a critical regulatory domain for protein complex formation, because when it is mutated, NHE3 binding to PLC-γ as well as NHERF2 is lost. An inhibitory peptide, which binds to the Src homology 2 domains contained in PLC-γ without interrupting binding of PLC-γ to NHE3, was used to probe a non-lipase-dependent role of PLC-γ. In the presence of this peptide, carbachol- stimulated calcium inhibition of NHE3 was lost. These results mirror previous studies with the transient receptor potential channel and suggest that PLC-γ may play a common role in regulating the cell-surface expression of ion transporters.

Original languageEnglish (US)
Pages (from-to)19437-19444
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number29
DOIs
StatePublished - Jul 17 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Phospholipase C-γ binds directly to the Na<sup>+</sup>/H<sup>+</sup> exchanger 3 and is required for calcium regulation of exchange activity'. Together they form a unique fingerprint.

  • Cite this