KRIP6: a novel BTB/kelch protein regulating function of kainate receptors.
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.
Laezza
Fernanda
F
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. flaezza@wustl.edu
Wilding
Timothy J
TJ
Sequeira
Sunitha
S
Coussen
Françoise
F
Zhang
Xue Zhao
XZ
Hill-Robinson
Rona
R
Mulle
Christophe
C
Huettner
James E
JE
Craig
Ann Marie
AM
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
D009419:Nerve Tissue Proteins; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor