title: Co-assembly of two GluR6 kainate receptor splice variants within a functional protein complex.
abstract: Kainate receptors (KAR) are composed of several distinct subunits and splice variants, but the functional relevance of this diversity remains largely unclear. Here we show that two splice variants of the GluR6 subunit, GluR6a and GluR6b, which differ in their C-terminal domains, do not show distinct functional properties, but coassemble as heteromers in vitro and in vivo. Using a proteomic approach combining affinity purification and MALDI-TOF mass spectrometry, we found that GluR6a and GluR6b interact with two distinct subsets of cytosolic proteins mainly involved in Ca(2+) regulation of channel function and intracellular trafficking. Guided by these results, we provide evidence that the regulation of native KAR function by NMDA receptors depends on the heteromerization of GluR6a and GluR6b and interaction of calcineurin with GluR6b. Thus, GluR6a and GluR6b bring in close proximity two separate subsets of interacting proteins that contribute to the fine regulation of KAR trafficking and function.
authors.affiliation: Laboratoire "Physiologie Cellulaire de la Synapse", CNRS, UMR 5091, Institut François Magendie, Université Bordeaux, 2, rue C. Saint-Saëns, 33077 Bordeaux Cedex, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Coussen
authors.forename: David
authors.initials: D
authors.lastname: Perrais
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jaskolski
authors.forename: Shankar
authors.initials: S
authors.lastname: Sachidhanandam
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Normand
authors.forename: Joel
authors.initials: J
authors.lastname: Bockaert
authors.forename: Philippe
authors.initials: P
authors.lastname: Marin
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D019703:Calcineurin / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D046911:Macromolecular Substances; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D000097806:GluK2 Kainate Receptor
chemical_list: D019703:Calcineurin; D007473:Ion Channels; D046911:Macromolecular Substances; D020033:Protein Isoforms; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor