title: Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering.
abstract: Several scaffold proteins for neurotransmitter receptors have been identified as candidates for receptor targeting. However, the molecular mechanism underlying such receptor clustering and targeting to postsynaptic specializations remains unknown. PSD-Zip45 (also named Homer 1c/vesl-1L) consists of the NH(2) terminus containing the enabled/VASP homology 1 domain and the COOH terminus containing the leucine zipper. Here, we demonstrate immunohistochemically that metabotropic glutamate receptor 1alpha (mGluR1alpha) and PSD-Zip45/Homer 1c are colocalized to synapses in the cerebellar molecular layer but not in the hippocampus. In cultured hippocampal neurons, PSD-Zip45/Homer1c and N-methyl-D-aspartate receptors are preferentially colocalized to dendritic spines. Cotransfection of mGluR1alpha or mGluR5 and PSD-Zip45/Homer 1c into COS-7 cells results in mGluR clustering induced by PSD-Zip45/Homer 1c. An in vitro multimerization assay shows that the extreme COOH-terminal leucine zipper is involved in self-multimerization of PSD-Zip45/Homer 1c. A clustering assay of mGluRs in COS-7 cells also reveals a critical role of this leucine-zipper motif of PSD-Zip45/Homer 1c in mGluR clustering. These results suggest that the leucine zipper of subsynaptic scaffold protein is a candidate motif involved in neurotransmitter receptor clustering at the central synapse.
authors.affiliation: Division of Neurochemistry, Department of Neuroscience, Osaka University Graduate School of Medicine, (C13) 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tadokoro
authors.forename: T
authors.initials: T
authors.lastname: Tachibana
authors.forename: T
authors.initials: T
authors.lastname: Imanaka
authors.forename: W
authors.initials: W
authors.lastname: Nishida
authors.forename: K
authors.initials: K
authors.lastname: Sobue
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D016350:Leucine Zippers; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011940:Receptor Aggregation; D018092:Kainic Acid Receptors / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1