title: KRIP6: a novel BTB/kelch protein regulating function of kainate receptors.
abstract: Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. flaezza@wustl.edu
authors.forename: Fernanda
authors.initials: F
authors.lastname: Laezza
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Wilding
authors.forename: Sunitha
authors.initials: S
authors.lastname: Sequeira
authors.forename: Françoise
authors.initials: F
authors.lastname: Coussen
authors.forename: Xue Zhao
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Rona
authors.initials: R
authors.lastname: Hill-Robinson
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.forename: James E
authors.initials: JE
authors.lastname: Huettner
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Craig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D019706:Excitatory Postsynaptic Potentials; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D051381:Rats; D018092:Kainic Acid Receptors / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000097806:GluK2 Kainate Receptor
chemical_list: D009419:Nerve Tissue Proteins; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor