Direct interaction of GluRdelta2 with Shank scaffold proteins in cerebellar Purkinje cells.
Glutamate receptor (GluR) delta2 selectively expressed in cerebellar Purkinje cells plays a central role in cerebellar long-term depression (LTD), motor learning, and formation of parallel fiber synapses. By yeast two-hybrid screening, we identified members of the Shank family of scaffold proteins as major GluRdelta2-interacting molecules. GluRdelta2 bound directly to the PDZ domain of Shank proteins through an internal motif in the carboxyl-terminal putative cytoplasmic domain. Shank1 and Shank2 proteins as well as GluRdelta2 proteins were localized in the dendritic spines of cultured Purkinje cells. Anti-GluRdelta2 antibodies immunoprecipitated Shank1, Shank2, Homer, and metabotropic GluR1alpha proteins from the synaptosomal membrane fractions of cerebella. Furthermore, Shank2 interacted with GRIP1 in the cerebellum. These results suggest that through Shank1 and Shank2, GluRdelta2 interacts with the metabotropic GluR1alpha, the AMPA-type GluR, and the inositol 1,4,5-trisphosphate receptor (IP3R) that are essential for cerebellar LTD.
Uemura
Takeshi
T
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, and Japan; SORST, Japan Science and Technology Corporation, Tokyo 113-0033, Japan.
Mori
Hisashi
H
Mishina
Masayoshi
M
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047908:Intracellular Signaling Peptides and Proteins; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D018160:Receptors, Cytoplasmic and Nuclear; D017470:Receptors, Glutamate; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; C120531:Shank1 protein, rat; C488222:Shank2 protein, mouse; C485686:Shank2 protein, rat; C107913:glutamate receptor delta 2