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

 Abstract

The Ins(1,4,5)P3 receptor acts as a central hub for Ca2+ 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)P3 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)P3-dependent Ca2+ release and lowers the Ins(1,4,5)P3 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.

Full Text Options
Article
Metrics
 Share
 Full Text
 Info
Pages
379 - 384
doi
10.4161/chan.21170
Type
Research Paper
 Metrics
 Cite This Article
 Permissions
Creative Commons License Permissions
 Reprints
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