Involvement of Unique Leucine-Zipper Motif of PSD-Zip45 (Homer 1c/vesl-1L) in Group 1 Metabotropic Glutamate Receptor Clustering

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 24; pp. 13801 - 13806
• Main Authors: Tadokoro, Satoko, Tachibana, Taro, Imanaka, Takanobu, Nishida, Wataru, Sobue, Kenji
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 23.11.1999; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antibodies; Biological Sciences; Brain - metabolism; Brain - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell membranes; Cellular biology; COS Cells; glutamic acid receptors; Hippocampus; Homer 1c/vesl-1L protein; Homer Scaffolding Proteins; Leucine Zippers; Mice; N methyl D aspartate receptors; Neurology; Neurons; Neuropeptides - genetics; Neuropeptides - metabolism; Plasmids; Postsynaptic density protein; Proteins; PSD-Zip45 protein; Rats; Rats, Sprague-Dawley; Receptor Aggregation; receptor clustering; Receptors; Receptors, Kainic Acid - genetics; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - metabolism; Scaffolds; Synapses; Zip45 protein
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.24.13801

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 NH2 terminus containing the enabled/VASP homology 1 domain and the COOH terminus containing the leucine zipper. Here, we demonstrate immunohistochemically that metabotropic glutamate receptor 1α (mGluR1α) 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 mGluR1α 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.