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. Academic Article uri icon

Overview

abstract

  • The Ins(1,4,5)P 3 receptor acts as a central hub for Ca ( 2+) signaling by integrating multiple signaling modalities into Ca ( 2+) 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)P 3 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)P 3-dependent Ca ( 2+) 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)P 3 receptor results in decreased Ins(1,4,5)P 3-dependent Ca ( 2+) 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)P 3-dependent Ca ( 2+) release during meiosis, argue that phosphorylation within the coupling domain of the Ins(1,4,5)P 3 receptor acts in a combinatorial fashion to regulate Ins(1,4,5)P 3 receptor function.

publication date

  • August 10, 2012

Research

keywords

  • Inositol 1,4,5-Trisphosphate
  • Inositol 1,4,5-Trisphosphate Receptors

Identity

PubMed Central ID

  • PMC3508777

Scopus Document Identifier

  • 84868105018

Digital Object Identifier (DOI)

  • 10.1242/dev.02624

PubMed ID

  • 22878752

Additional Document Info

volume

  • 6

issue

  • 5