DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity |
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Authors: | van Rossum Damian B Patterson Randen L Cheung King-Ho Barrow Roxanne K Syrovatkina Viktoriya Gessell Gregory S Burkholder Scott G Watkins D Neil Foskett J Kevin Snyder Solomon H |
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Institution: | Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA. |
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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. |
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