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, David Neil Watkins, J Kevin Foskett, Solomon H Snyder

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38 Citations (Scopus)

Abstract

We report the cloning and characterization of DANGER, a novel protein which physiologically binds to inositol 1,4,5-trisphosphate receptors (IP(3)R). 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 IP(3)R. DANGER interacts with IP(3)R in vitro and co-immunoprecipitates with IP(3)R from cellular preparations. DANGER robustly enhances Ca(2+)-mediated inhibition of IP(3) RCa(2+) release without affecting IP(3) binding in microsomal assays and inhibits gating in single-channel recordings of IP(3)R. DANGER appears to allosterically modulate the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed.
Original languageEnglish
Pages (from-to)37111 - 37116
Number of pages6
JournalJournal of Biological Chemistry
Volume281
Issue number48
Publication statusPublished - 2006
Externally publishedYes

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