DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity

Damian B. Van Rossum, Randen L. Patterson, King Ho Cheung, Roxanne K. Barrow, Viktoriya Syrovatkina, Gregory S. Gessell, Scott G. Burkholder, D. Neil Watkins, J. Kevin Foskett, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP 3R). DANGER is a membrane-associated protein predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages where it localizes to membranes in the cell periphery together with IP3R. DANGER interacts with IP3R in vitro and co-immunoprecipitates with IP3R from cellular preparations. DANGER robustly enhances Ca2+-mediated inhibition of IP3R Ca 2+ release without affecting IP3 binding in microsomal assays and inhibits gating in single-channel recordings of IP3R. DANGER appears to allosterically modulate the sensitivity of IP3R to Ca2+ inhibition, which likely alters IP3R-mediated Ca 2+ dynamics in cells where DANGER and IP3R are co-expressed.

Original languageEnglish (US)
Pages (from-to)37111-37116
Number of pages6
JournalJournal of Biological Chemistry
Volume281
Issue number48
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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