Cited by 862Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingIon channel regulation and function

Homer Binds a Novel Proline-Rich Motif and Links Group 1 Metabotropic Glutamate Receptors with IP3 Receptors

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Tu, Jian Cheng, Xiao, Bo, Yuan, Joseph P, Lanahan, Anthony A, Leoffert, Kathleen, Li, Min, Linden, David J, Worley, Paul F·1998·Neuron

Abstract

Group I metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich "Homer ligand" (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.

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Crossref · 10.1016/s0896-6273(00)80589-9

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  • HOMER1 is engaged in NeuN+ specific peaks and loops and its expression is significantly higher in NeuN+ cells compared with NeuN− cells.

    “For example, a gene that encodes a synaptic scaffolding protein, HOMER132, was engaged in NeuN+ specific peaks and loops and its expression was significantly higher in NeuN+ cells compared with NeuN− cells (Fig. 2b).”

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Authors
Tu, J. C., Xiao, B., Yuan, J. P., Lanahan, A. A., Leoffert, K., Li, M., Linden, D. J., & Worley, P. F.
Affiliations
Johns Hopkins University (US)
Corresponding author
Worley, Paul F
Venue
Neuron
Publisher
Elsevier BV
Published
1998-10
Volume
21
Issue
4
Pages
717-726
ISSN
0896-6273 (ISSN-L)
OpenAlex
W2164762131
Cited by
862
References
68
Citations by year
2026: 14 · 2025: 7 · 2024: 12 · 2023: 6 · 2022: 21 · 2021: 23 · 2020: 12 · 2019: 19 · 2018: 23 · 2017: 32 · 2016: 23 · 2015: 23 · 2014: 27 · 2013: 36 · 2012: 41
FWCI
15.70
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Genentech
  • National Institute of Mental Health (K02MH001152, KO2 MH01152)
  • National Institute on Drug Abuse (DA 10309, DA 11742, R01DA011742)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
Homer proteins, group I metabotropic glutamate receptors, IP3 receptor, proline-rich motif, receptor complex formation, intracellular calcium release, calcium signaling, immediate early genes, synaptic proteins
MeSH terms
Homer Scaffolding Proteins, Amino Acid Sequence, Animals, Calcium, Carrier Proteins, Intracellular Membranes, Ligands, Molecular Sequence Data, Neuropeptides, Proline, Time Factors, Calcium Channels, Gene Expression, Genes, Immediate-Early, Receptors, Metabotropic Glutamate, Receptors, Cytoplasmic and Nuclear, Glutamic Acid, GTP Phosphohydrolases, Dynamins, Rats, Inositol 1,4,5-Trisphosphate Receptors

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