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

DB Van Rossum, RL Patterson, King-Ho CHEUNG, RK Barrow, V Syrovatkina, GS Gessell, SG Burkholder, DN Watkins, JK Foskett, SH Snyder

Research output: Contribution to journalArticlepeer-review

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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)37111-37116
Number of pages5
JournalJournal of Biological Chemistry
Volume281
Issue number48
DOIs
Publication statusPublished - 2006

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