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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2003 Apr 29;358(1432):715–720. doi: 10.1098/rstb.2002.1215

GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity.

Fabrice Duprat 1, Michael Daw 1, Wonil Lim 1, Graham Collingridge 1, John Isaac 1
PMCID: PMC1693166  PMID: 12740117

Abstract

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

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Selected References

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  1. Beattie E. C., Carroll R. C., Yu X., Morishita W., Yasuda H., von Zastrow M., Malenka R. C. Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci. 2000 Dec;3(12):1291–1300. doi: 10.1038/81823. [DOI] [PubMed] [Google Scholar]
  2. Boudin H., Doan A., Xia J., Shigemoto R., Huganir R. L., Worley P., Craig A. M. Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron. 2000 Nov;28(2):485–497. doi: 10.1016/s0896-6273(00)00127-6. [DOI] [PubMed] [Google Scholar]
  3. Bowie D., Mayer M. L. Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron. 1995 Aug;15(2):453–462. doi: 10.1016/0896-6273(95)90049-7. [DOI] [PubMed] [Google Scholar]
  4. Braithwaite S. P., Meyer G., Henley J. M. Interactions between AMPA receptors and intracellular proteins. Neuropharmacology. 2000 Apr 3;39(6):919–930. doi: 10.1016/s0028-3908(99)00171-9. [DOI] [PubMed] [Google Scholar]
  5. Braithwaite Steven P., Xia Houhui, Malenka Robert C. Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proc Natl Acad Sci U S A. 2002 May 14;99(10):7096–7101. doi: 10.1073/pnas.102156099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brusa R., Zimmermann F., Koh D. S., Feldmeyer D., Gass P., Seeburg P. H., Sprengel R. Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science. 1995 Dec 8;270(5242):1677–1680. doi: 10.1126/science.270.5242.1677. [DOI] [PubMed] [Google Scholar]
  7. Burnashev N., Monyer H., Seeburg P. H., Sakmann B. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron. 1992 Jan;8(1):189–198. doi: 10.1016/0896-6273(92)90120-3. [DOI] [PubMed] [Google Scholar]
  8. Carroll R. C., Lissin D. V., von Zastrow M., Nicoll R. A., Malenka R. C. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nat Neurosci. 1999 May;2(5):454–460. doi: 10.1038/8123. [DOI] [PubMed] [Google Scholar]
  9. Chung H. J., Xia J., Scannevin R. H., Zhang X., Huganir R. L. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci. 2000 Oct 1;20(19):7258–7267. doi: 10.1523/JNEUROSCI.20-19-07258.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Daw M. I., Chittajallu R., Bortolotto Z. A., Dev K. K., Duprat F., Henley J. M., Collingridge G. L., Isaac J. T. PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses. Neuron. 2000 Dec;28(3):873–886. doi: 10.1016/s0896-6273(00)00160-4. [DOI] [PubMed] [Google Scholar]
  11. Dev K. K., Nakajima Y., Kitano J., Braithwaite S. P., Henley J. M., Nakanishi S. PICK1 interacts with and regulates PKC phosphorylation of mGLUR7. J Neurosci. 2000 Oct 1;20(19):7252–7257. doi: 10.1523/JNEUROSCI.20-19-07252.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dev K. K., Nishimune A., Henley J. M., Nakanishi S. The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology. 1999 May;38(5):635–644. doi: 10.1016/s0028-3908(98)00230-5. [DOI] [PubMed] [Google Scholar]
  13. Dong H., O'Brien R. J., Fung E. T., Lanahan A. A., Worley P. F., Huganir R. L. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature. 1997 Mar 20;386(6622):279–284. doi: 10.1038/386279a0. [DOI] [PubMed] [Google Scholar]
  14. Duggan Anne, Garcia-Anoveros Jaime, Corey David P. The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons. J Biol Chem. 2001 Dec 5;277(7):5203–5208. doi: 10.1074/jbc.M104748200. [DOI] [PubMed] [Google Scholar]
  15. El Far O., Airas J., Wischmeyer E., Nehring R. B., Karschin A., Betz H. Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK1. Eur J Neurosci. 2000 Dec;12(12):4215–4221. doi: 10.1046/j.1460-9568.2000.01309.x. [DOI] [PubMed] [Google Scholar]
  16. Hayashi Y., Shi S. H., Esteban J. A., Piccini A., Poncer J. C., Malinow R. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science. 2000 Mar 24;287(5461):2262–2267. doi: 10.1126/science.287.5461.2262. [DOI] [PubMed] [Google Scholar]
  17. Hruska-Hageman Alesia M., Wemmie John A., Price Margaret P., Welsh Michael J. Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). Biochem J. 2002 Feb 1;361(Pt 3):443–450. doi: 10.1042/0264-6021:3610443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jia Z., Agopyan N., Miu P., Xiong Z., Henderson J., Gerlai R., Taverna F. A., Velumian A., MacDonald J., Carlen P. Enhanced LTP in mice deficient in the AMPA receptor GluR2. Neuron. 1996 Nov;17(5):945–956. doi: 10.1016/s0896-6273(00)80225-1. [DOI] [PubMed] [Google Scholar]
  19. Kamboj S. K., Swanson G. T., Cull-Candy S. G. Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors. J Physiol. 1995 Jul 15;486(Pt 2):297–303. doi: 10.1113/jphysiol.1995.sp020812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee Sang Hyoung, Liu Lidong, Wang Yu Tian, Sheng Morgan. Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron. 2002 Nov 14;36(4):661–674. doi: 10.1016/s0896-6273(02)01024-3. [DOI] [PubMed] [Google Scholar]
  21. Li P., Kerchner G. A., Sala C., Wei F., Huettner J. E., Sheng M., Zhuo M. AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses. Nat Neurosci. 1999 Nov;2(11):972–977. doi: 10.1038/14771. [DOI] [PubMed] [Google Scholar]
  22. Lu W., Man H., Ju W., Trimble W. S., MacDonald J. F., Wang Y. T. Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron. 2001 Jan;29(1):243–254. doi: 10.1016/s0896-6273(01)00194-5. [DOI] [PubMed] [Google Scholar]
  23. Lüscher C., Nicoll R. A., Malenka R. C., Muller D. Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci. 2000 Jun;3(6):545–550. doi: 10.1038/75714. [DOI] [PubMed] [Google Scholar]
  24. Lüscher C., Xia H., Beattie E. C., Carroll R. C., von Zastrow M., Malenka R. C., Nicoll R. A. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron. 1999 Nov;24(3):649–658. doi: 10.1016/s0896-6273(00)81119-8. [DOI] [PubMed] [Google Scholar]
  25. Lüthi A., Chittajallu R., Duprat F., Palmer M. J., Benke T. A., Kidd F. L., Henley J. M., Isaac J. T., Collingridge G. L. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron. 1999 Oct;24(2):389–399. doi: 10.1016/s0896-6273(00)80852-1. [DOI] [PubMed] [Google Scholar]
  26. Matsuda S., Launey T., Mikawa S., Hirai H. Disruption of AMPA receptor GluR2 clusters following long-term depression induction in cerebellar Purkinje neurons. EMBO J. 2000 Jun 15;19(12):2765–2774. doi: 10.1093/emboj/19.12.2765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nishimune A., Isaac J. T., Molnar E., Noel J., Nash S. R., Tagaya M., Collingridge G. L., Nakanishi S., Henley J. M. NSF binding to GluR2 regulates synaptic transmission. Neuron. 1998 Jul;21(1):87–97. doi: 10.1016/s0896-6273(00)80517-6. [DOI] [PubMed] [Google Scholar]
  28. Noel J., Ralph G. S., Pickard L., Williams J., Molnar E., Uney J. B., Collingridge G. L., Henley J. M. Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron. 1999 Jun;23(2):365–376. doi: 10.1016/s0896-6273(00)80786-2. [DOI] [PubMed] [Google Scholar]
  29. Osten P., Khatri L., Perez J. L., Köhr G., Giese G., Daly C., Schulz T. W., Wensky A., Lee L. M., Ziff E. B. Mutagenesis reveals a role for ABP/GRIP binding to GluR2 in synaptic surface accumulation of the AMPA receptor. Neuron. 2000 Aug;27(2):313–325. doi: 10.1016/s0896-6273(00)00039-8. [DOI] [PubMed] [Google Scholar]
  30. Osten P., Srivastava S., Inman G. J., Vilim F. S., Khatri L., Lee L. M., States B. A., Einheber S., Milner T. A., Hanson P. I. The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs. Neuron. 1998 Jul;21(1):99–110. doi: 10.1016/s0896-6273(00)80518-8. [DOI] [PubMed] [Google Scholar]
  31. Passafaro M., Piëch V., Sheng M. Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat Neurosci. 2001 Sep;4(9):917–926. doi: 10.1038/nn0901-917. [DOI] [PubMed] [Google Scholar]
  32. Perez J. L., Khatri L., Chang C., Srivastava S., Osten P., Ziff E. B. PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci. 2001 Aug 1;21(15):5417–5428. doi: 10.1523/JNEUROSCI.21-15-05417.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pickard L., Noël J., Duckworth J. K., Fitzjohn S. M., Henley J. M., Collingridge G. L., Molnar E. Transient synaptic activation of NMDA receptors leads to the insertion of native AMPA receptors at hippocampal neuronal plasma membranes. Neuropharmacology. 2001 Nov;41(6):700–713. doi: 10.1016/s0028-3908(01)00127-7. [DOI] [PubMed] [Google Scholar]
  34. Sheng M., Lee S. H. AMPA receptor trafficking and the control of synaptic transmission. Cell. 2001 Jun 29;105(7):825–828. doi: 10.1016/s0092-8674(01)00406-8. [DOI] [PubMed] [Google Scholar]
  35. Song I., Kamboj S., Xia J., Dong H., Liao D., Huganir R. L. Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron. 1998 Aug;21(2):393–400. doi: 10.1016/s0896-6273(00)80548-6. [DOI] [PubMed] [Google Scholar]
  36. Srivastava S., Osten P., Vilim F. S., Khatri L., Inman G., States B., Daly C., DeSouza S., Abagyan R., Valtschanoff J. G. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron. 1998 Sep;21(3):581–591. doi: 10.1016/s0896-6273(00)80568-1. [DOI] [PubMed] [Google Scholar]
  37. Staudinger J., Zhou J., Burgess R., Elledge S. J., Olson E. N. PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system. J Cell Biol. 1995 Feb;128(3):263–271. doi: 10.1083/jcb.128.3.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Torres R., Firestein B. L., Dong H., Staudinger J., Olson E. N., Huganir R. L., Bredt D. S., Gale N. W., Yancopoulos G. D. PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron. 1998 Dec;21(6):1453–1463. doi: 10.1016/s0896-6273(00)80663-7. [DOI] [PubMed] [Google Scholar]
  39. Wang Y. T., Linden D. J. Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron. 2000 Mar;25(3):635–647. doi: 10.1016/s0896-6273(00)81066-1. [DOI] [PubMed] [Google Scholar]
  40. Weiss J. H., Sensi S. L. Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci. 2000 Aug;23(8):365–371. doi: 10.1016/s0166-2236(00)01610-6. [DOI] [PubMed] [Google Scholar]
  41. Xia J., Chung H. J., Wihler C., Huganir R. L., Linden D. J. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron. 2000 Nov;28(2):499–510. doi: 10.1016/s0896-6273(00)00128-8. [DOI] [PubMed] [Google Scholar]
  42. Xia J., Zhang X., Staudinger J., Huganir R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron. 1999 Jan;22(1):179–187. doi: 10.1016/s0896-6273(00)80689-3. [DOI] [PubMed] [Google Scholar]

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