title: DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity.
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.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.forename: Randen L
authors.initials: RL
authors.lastname: Patterson
authors.forename: King-Ho
authors.initials: KH
authors.lastname: Cheung
authors.forename: Roxanne K
authors.initials: RK
authors.lastname: Barrow
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Syrovatkina
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Gessell
authors.forename: Scott G
authors.initials: SG
authors.lastname: Burkholder
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Foskett
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000495:Allosteric Site; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D007313:Insecta; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D014357:Trypsin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
chemical_list: C516570:ITPRIP protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D014357:Trypsin; D002118:Calcium