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

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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

DOI 10.1016/s0896-6273(00)80589-9

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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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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
ORCID: Xiao, Bo
Li, Min
Linden, David J
Worley, Paul F
Venue: Neuron
Publisher: Elsevier BV
Published: 1998-10
Volume: 21
Issue: 4
Pages: 717-726
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(00)80589-9
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: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 923 d)
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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Homer Binds a Novel Proline-Rich Motif and Links Group 1 Metabotropic Glutamate Receptors with IP3 Receptors

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