Purified inositol 1,4,5-trisphosphate receptor mediates calcium flux in reconstituted lipid vesicles

Christopher D. Ferris, Richard L. Huganir, Surachai Supattapone, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

INOSITOL 1,4,5-trisphosphate (Ins (1,4,5)P3), a second messenger molecule involved in actions of neurotransmitters, hormones and growth factors, releases calcium from vesicular non-mitochondrial intracellular stores1. An Ins(1,4,5)P3 binding protein, purified from brain membranes2, has been shown to be phosphorylated by cyclic-AMP-dependent protein kinase3 and localized by immunohistochemical techniques to intracellular particles associated with the endoplasmic reticulum4. Although the specificity of the Ins(1,4,5)P3 binding protein for inositol phosphates and the high affinity of the protein for Ins(1,4,5)P3 indicate that it is a physiological Ins(1,4,5)P3 receptor mediating calcium release, direct evidence for this has been difficult to obtain. Also, it is unclear whether a single protein mediates both the recognition of Ins(1,4,5)P3 and calcium transport or whether these two functions involve two or more distinct proteins. In the present study we report reconstitution of the purified Ins(1,4,5)P3 binding protein into lipid vesicles. We show that Ins(1,4,5)P3 and other inositol phosphates stimulate calcium flux in the reconstituted vesicles with potencies and specificities that match the calcium releasing actions of Ins(1,4,5)P3. These results indicate that the purified Ins(1,4,5)P3 binding protein is a physiological receptor responsible for calcium release.

Original languageEnglish (US)
Pages (from-to)87-89
Number of pages3
JournalNature
Volume342
Issue number6245
DOIs
StatePublished - Jan 1 1989

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