Homer Binds a Novel Proline-Rich Motif and Links Group 1 Metabotropic Glutamate Receptors with IP3 Receptors
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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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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).”
From Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders (2021) · cites this paper as [32]
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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
- hybrid
- doi.org
- Licence
- 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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