Heteromer formation of δ2 glutamate receptors with AMPA or kainate receptors

Kazuhisa Kohda, Yoshinori Kamiya, Shinji Matsuda, Kunio Kato, Hisashi Umemori, Michisuke Yuzaki

研究成果: Article査読

30 被引用数 (Scopus)


The δ2 glutamate receptor (GluRδ2) is predominantly expressed in the postsynaptic densities of parallel fiber-Purkinje cell synapses and plays a crucial role in cerebellar function. However, the mechanisms by which GluRδ2 participates in cerebellar functions are largely unknown because GluRδ2 does not bind glutamate analogs. We investigated the possibility that GluRδ2 may be involved in channel formation together with other glutamate receptor families. We transiently expressed lurcher mutant AMPA receptor GluR1Lc and kainate receptor GluR6Lc in HEK293 cells. Cells expressing these constitutively active channels displayed a rectifying current-voltage (I-V) relationship. However, when cells were co-transfected with GluRδ2Lc, which had the arginine residue in the channel pore region, cells displayed a linear I-V relationship, a result that indicates GluRδ2Lc formed functional heteromeric channels with GluR1Lc or GluR6Lc. Assembly of GluRδ2 with GluR1 or GluR6 was further confirmed by co-immunoprecipitation assays in HEK293 cells. In addition, GluRδ2 receptors were partially co-immunoprecipitated from cerebellar synaptosomal fractions by antibodies against GluR2 or KA2. In contrast to lurcher channels, expression of wild-type GluRδ2 significantly reduced the glutamate-induced current of the wild-type GluR1 receptors without affecting channel properties, such as current kinetics, dose-response relationship, and single-channel conductance. Thus, the heteromeric channel created by the association of wild-type GluR1 and GluRδ2 may not be gated by glutamate and does not participate in glutamate-induced currents. These results suggest that GluRδ2 and AMPA or kainate receptors can assemble to form heteromeric receptors in vitro and could modify glutamate signaling in vivo. These findings may help explain the role of GluRδ2.

ジャーナルMolecular Brain Research
出版ステータスPublished - 2003 1月 31

ASJC Scopus subject areas

  • 分子生物学
  • 細胞および分子神経科学


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