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- Published:
Homer: a protein that selectively binds metabotropic glutamate receptors
- P. R. Brakeman1,
- A. A. Lanahan1,
- Richard O'Brien1,2,
- K. Roche5,
- C. A. Barnes6,
- R. L. Huganir1,3,4 &
- …
- P. F. Worley1,2
Naturevolume 386, pages284–288 (1997)Cite this article
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Abstract
Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors1 and ion channels2. PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them. Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. TheHomer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.
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References
Kornau, H. C., Schenker, L. T., Kennedy, M. B. & Seeburg, P. H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.Science269, 1737–1740 (1995).
Kim, E., Niethammer, M., Rothschild, A., Jan, Y. N. & Sheng, M. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.Nature378, 85–88 (1995).
Goelet, P., Castellucci, V., Schlacher, S. & Kandel, E. The long and the short of long-term memory—a molecular framework.Nature322, 419–422 (1986).
Nguyen, P. V., Abel, T. & Kandel, E. R. Requirement of a critical period of transcription for induction of a late phase of LTP.Science265, 1104–1107 (1994).
Nedivi, E., Hevroni, D., Naot, D., Israeli, D. & Citri, Y. Numerous candidate plasticity-related genes revealed by differential cDNA cloning.Nature363, 713–722 (1993).
Qian, Z., Gilbert, M. E., Colicos, M. A., Kandel, E. R. & Kuhl, D. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation.Nature361, 453–457 (1993).
Yamagata, K., Andreasson, K. I., Kaufmann, W. E., Barnes, C. A. & Worley, P. F. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids.Neuron11, 371–386 (1993).
Yamagata, K.et al. Rheb, a growth factor and synaptic activity regulated gene, encodes a novel Ras-related protein.J. Biol. Chem.269, 16333–16339 (1994).
Lyford, G.et al.Arc, a growth factor and activity-regulated gene encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites.Neuron14, 433–445 (1995).
Tsui, C.et al.Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity.J. Neurosci.16, 2463–2478 (1996).
Shaw, G. & Kamen, R. A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation.Cell46, 659–667 (1986).
Doyle, D. A.et al. Crystal structures of a complexed and peptide-free membrane protein-binding domain—molecular basis of peptide recognition by PDZ.Cell85, 1067–1076 (1996).
Nakanishi, S. Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity.Neuron13, 1031–1037 (1994).
Pin, J. P. & Duvoisin, R. The metabotropic glutamate receptors: structure and functions.Neuropharmacology34, 1–26 (1995).
Romano, C.et al. Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain.Comp. Neurol.355, 455–469 (1995).
Martin, L. J., Blackstone, C. D., Huganir, R. L. & Price, D. L. Cellular localization of a metabotropic glutamate receptor in rat brain.Neuron9, 259–270 (1992).
Worley, P. F.et al. Synaptic regulation of immediate early genes in brain.Cold Spring Harb. Symp. Quant. Biol.55, 213–223 (1990).
Hyman, S. E., Cole, R. L., Konradi, C. & Kosofsky, B. E. Dopamine regulation of transcription factor-target interactions in rat striatum.Chem. Senses20, 257–260 (1995).
Bhat, R. V. & Baraban, J. M. Activation of transcription factor genes in striatum by cocaine: role of both serotonin and dopamine systems.J. Pharmacol. Exp. Ther.267, 496–505 (1993).
Pin, J. P., Joly, C., Heinemann, S. F. & Bockaert, J. Domains involved in the specificity of G protein activation in phospholipase C-coupled metabotropic glutamate receptors.EMBO J.13, 342–348 (1994).
Joly, C.et al. Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluRl.J. Neurosci.15, 3970–3981 (1995).
Flor, P. J.et al. The C-terminal domain of the mGluRl metabotropic glutamate receptor affects sensitivity to agonists.J. Neurochem.67, 58–63 (1996).
Baude, A.et al. The metabotropic glutamate receptor (mGluRlα) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction.Neuron11, 771–787 (1993).
Nusser, Z., Mulvihill, E., Streit, P. & Somogyi, P. Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization.Neuroscience61, 421–427 (1994).
Yee, W. & Worley, P. F. Rheb interacts with Raf-1 kinase and may function to integrate growth factor-and protein kinase A-dependent signals.Mol. Cell. Biol.17, 921–933 (1997).
Chevray, P. M. & Nathans, D. Protein-interaction cloning in yeast—identification of mammalian proteins that react with the leucine zipper of Jun.Proc. Nat. Acad. Sci. USA89, 5789–5792 (1992).
Dong, H.et al. GRIP: a synaptic PD2 domain-containing protein that interacts with AMPA receptorsNature386, 279–284 (1997).
Worley, P. F.et al. Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement.J. Neurosci.13, 4776–4786 (1993).
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Authors and Affiliations
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
P. R. Brakeman, A. A. Lanahan, Richard O'Brien, R. L. Huganir & P. F. Worley
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
Richard O'Brien & P. F. Worley
Department of Biochemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
R. L. Huganir
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA
R. L. Huganir
National Institutes of Health, Bethesda, Maryland, 20892, USA
K. Roche
Department of Psychology and Neurology and Division of Neuronal Systems, Memory, and Aging, University of Arizona, Tucson, Arizona, 84724, USA
C. A. Barnes
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Brakeman, P., Lanahan, A., O'Brien, R.et al. Homer: a protein that selectively binds metabotropic glutamate receptors.Nature386, 284–288 (1997). https://doi.org/10.1038/386284a0
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