Home LiteratureArticle Details
PMID: 10570153 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 24 ·1999-11-23 ·Pages 13801-6

Tadokoro S, Tachibana T, Imanaka T, Nishida W, Sobue K

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.

MeSH Terms
Animals Brain/metabolism,pathology COS Cells Carrier Proteins/genetics,metabolism Homer Scaffolding Proteins Leucine Zippers Mice Neuropeptides/genetics,metabolism Rats Rats, Sprague-Dawley Receptor Aggregation Receptors, Kainic Acid/genetics Receptors, Metabotropic Glutamate/genetics,metabolism
Chemicals
Carrier Proteins Gluk1 kainate receptor Homer Scaffolding Proteins Neuropeptides Receptors, Kainic Acid Receptors, Metabotropic Glutamate metabotropic glutamate receptor type 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Tadokoro S
Division of Neurochemistry, Department of Neuroscience, Osaka University Graduate School of Medicine, (C13) 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tachibana T
Imanaka T
Nishida W
Sobue K
References (30)
30 references, click to expand
  1. pEF-BOS, a powerful mammalian expression vector.
    Nucleic Acids Res. 1990 Sep 11;18(17):5322 PMID: 1698283
  2. Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly.
    Cell. 1999 May 14;97(4):471-80 PMID: 10338211
  3. Mutagenesis of the 43-kD postsynaptic protein defines domains involved in plasma membrane targeting and AChR clustering.
    J Cell Biol. 1991 Dec;115(6):1713-23 PMID: 1757470
  4. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction.
    J Biol Chem. 1992 Jul 5;267(19):13361-8 PMID: 1320017
  5. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain.
    J Comp Neurol. 1995 May 8;355(3):455-69 PMID: 7636025
  6. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.
    Science. 1995 Sep 22;269(5231):1737-40 PMID: 7569905
  7. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.
    Nature. 1995 Nov 2;378(6552):85-8 PMID: 7477295
  8. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins.
    Neuron. 1996 Jul;17(1):103-13 PMID: 8755482
  9. Coiled coils: new structures and new functions.
    Trends Biochem Sci. 1996 Oct;21(10):375-82 PMID: 8918191
  10. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules.
    J Cell Biol. 1997 Feb 10;136(3):669-78 PMID: 9024696
  11. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors.
    Nature. 1997 Mar 20;386(6622):279-84 PMID: 9069286
  12. Homer: a protein that selectively binds metabotropic glutamate receptors.
    Nature. 1997 Mar 20;386(6622):284-8 PMID: 9069287
  13. SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density.
    J Biol Chem. 1997 May 2;272(18):11943-51 PMID: 9115257
  14. Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95.
    Neuron. 1997 May;18(5):803-14 PMID: 9182804
  15. vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis.
    FEBS Lett. 1997 Jul 21;412(1):183-9 PMID: 9257717
  16. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus.
    J Neurosci. 1997 Oct 1;17(19):7503-22 PMID: 9295396
  17. Dystrobrevin and dystrophin: an interaction through coiled-coil motifs.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12413-8 PMID: 9356463
  18. Differential expression of isoforms of PSD-95 binding protein (GKAP/SAPAP1) during rat brain development.
    FEBS Lett. 1997 Dec 1;418(3):301-4 PMID: 9428732
  19. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4.
    Neuron. 1998 Jan;20(1):125-34 PMID: 9459448
  20. Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors.
    J Biol Chem. 1998 Sep 11;273(37):23969-75 PMID: 9727012
  21. Activity and synaptic receptor targeting: the long view.
    Neuron. 1998 Sep;21(3):459-62 PMID: 9768832
  22. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP.
    Neuron. 1998 Sep;21(3):581-91 PMID: 9768844
  23. Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.
    Neuron. 1998 Oct;21(4):707-16 PMID: 9808458
  24. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.
    Neuron. 1998 Oct;21(4):717-26 PMID: 9808459
  25. Isolation of PSD-Zip45, a novel Homer/vesl family protein containing leucine zipper motifs, from rat brain.
    FEBS Lett. 1998 Oct 23;437(3):304-8 PMID: 9824313
  26. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.
    Nature. 1998 Dec 3;396(6710):433-9 PMID: 9853749
  27. Spatial control of actin filament assembly: lessons from Listeria.
    Cell. 1998 Dec 11;95(6):741-8 PMID: 9865692
  28. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1.
    Neuron. 1999 Jan;22(1):179-87 PMID: 10027300
  29. Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs.
    Neuron. 1999 Mar;22(3):497-509 PMID: 10197530
  30. Sequence and expression of a metabotropic glutamate receptor.
    Nature. 1991 Feb 28;349(6312):760-5 PMID: 1847995
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.24.13801
Published
1999-11-23
Pages
13801-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24145
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.24.13801 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2