Phosphorylation of the rat Ins(1,4,5)P3 receptor at T930 within the coupling domain decreases its affinity to Ins(1,4,5)P3

Shirley Haun, Lu Sun, Satanay Zuhair Hubrack, David Yule, Khaled Machaca

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The Ins(1,4,5)P3 receptor acts as a central hub for Ca 2+ signaling by integrating multiple signaling modalities into Ca2+ release from intracellular stores downstream of G-protein and tyrosine kinase-coupled receptor stimulation. As such, the Ins(1,4,5)P 3 receptor plays fundamental roles in cellular physiology. The regulation of the Ins(1,4,5)P3 receptor is complex and involves protein-protein interactions, post-translational modifications, allosteric modulation, and regulation of its sub-cellular distribution. Phosphorylation has been implicated in the sensitization of Ins(1,4,5)P3-dependent Ca2+ release observed during oocyte maturation. Here we investigate the role of phosphorylation at T-930, a residue phosphorylated specifically during meiosis. We show that a phosphomimetic mutation at T-930 of the rat Ins(1,4,5)P3 receptor results in decreased Ins(1,4,5)P 3-dependent Ca2+ release and lowers the Ins(1,4,5)P 3 binding affinity of the receptor. These data, coupled to the sensitization of Ins(1,4,5)P3-dependent Ca2+ release during meiosis, argue that phosphorylation within the coupling domain of the Ins(1,4,5)P3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P3 receptor function.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalChannels
Volume6
Issue number5
DOIs
Publication statusPublished - 2012

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Keywords

  • Affinity
  • Phosphomimetic
  • Phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Medicine(all)
  • Biochemistry

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