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AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse

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Abstract

Glutamate receptor trafficking in and out of synapses is one of the core mechanisms for rapid changes in the number of functional receptors during synaptic plasticity. Recent data have shown that the fast gain and loss of receptors from synaptic sites are accounted for by endocytic/exocytic processes and by their lateral diffusion in the plane of the membrane. These events are interdependent and regulated by neuronal activity and interactions with scaffolding proteins. We review here the main cellular steps for AMPA and NMDA receptor synthesis, traffic within intracellular organelles, membrane exocytosis/endocytosis and surface trafficking. We focus on new findings that shed light on the regulation of receptor cycling events and surface trafficking and the way that this might reshape our thinking about the specific regulation of receptor accumulation at synapses.

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References

  • Adesnik H, Nicoll RA, England PM (2005) Photoinactivation of native AMPA receptors reveals their real-time trafficking. Neuron 48:977–985

    PubMed  CAS  Google Scholar 

  • Ashby MC, De La Rue SA, Ralph GS, Uney J, Collingridge GL, Henley JM (2004) Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs. J Neurosci 24:5172–5176

    PubMed  CAS  Google Scholar 

  • Axelrod D, Ravdin P, Koppel DE, Schlessinger J, Webb WW, Elson EL, Podleski TR (1976) Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers. Proc Natl Acad Sci USA 73:4594–4598

    PubMed  CAS  Google Scholar 

  • Bagal AA, Kao JP, Tang CM, Thompson SM (2005) Long-term potentiation of exogenous glutamate responses at single dendritic spines. Proc Natl Acad Sci USA 102:14434–14439

    PubMed  CAS  Google Scholar 

  • Barria A, Derkach V, Soderling T (1997a) Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor. J Biol Chem 272:32727–32730

    PubMed  CAS  Google Scholar 

  • Barria A, Muller D, Derkach V, Griffith LC, Soderling TR (1997b) Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science 276:2042–2045

    PubMed  CAS  Google Scholar 

  • Bear MF, Malenka RC (1994) Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol 4:389–399

    PubMed  CAS  Google Scholar 

  • Beattie EC, Carroll RC, Yu X, Morishita W, Yasuda H, Zastrow M von, Malenka RC (2000) Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci 3:1291–1300

    PubMed  CAS  Google Scholar 

  • Benke TA, Luthi A, Isaac JT, Collingridge GL (1998) Modulation of AMPA receptor unitary conductance by synaptic activity. Nature 393:793–797

    PubMed  CAS  Google Scholar 

  • Beretta F, Sala C, Saglietti L, Hirling H, Sheng M, Passafaro M (2005) NSF interaction is important for direct insertion of GluR2 at synaptic sites. Mol Cell Neurosci 28:650–660

    PubMed  CAS  Google Scholar 

  • Blanpied TA, Scott DB, Ehlers MD (2002) Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines. Neuron 36:435–449

    PubMed  CAS  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    PubMed  CAS  Google Scholar 

  • Bloodgood BL, Sabatini BL (2005) Neuronal activity regulates diffusion across the neck of dendritic spines. Science 310:866–869

    PubMed  CAS  Google Scholar 

  • Bolshakov VY, Carboni L, Cobb MH, Siegelbaum SA, Belardetti F (2000) Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3-CA1 synapses. Nat Neurosci 3:1107–1112

    PubMed  CAS  Google Scholar 

  • Borgdorff A, Choquet D (2002) Regulation of AMPA receptor lateral movement. Nature 417:649–653

    PubMed  CAS  Google Scholar 

  • Bredt DS, Nicoll RA (2003) AMPA receptor trafficking at excitatory synapses. Neuron 40:361–379

    PubMed  CAS  Google Scholar 

  • Brown TC, Tran IC, Backos DS, Esteban JA (2005) NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron 45:81–94

    PubMed  CAS  Google Scholar 

  • Carroll RC, Zukin RS (2002) NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity. Trends Neurosci 25:571–577

    PubMed  CAS  Google Scholar 

  • Carroll RC, Lissin DV, Zastrow M von, Nicoll RA, Malenka RC (1999a) Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nat Neurosci 2:454–460

    PubMed  CAS  Google Scholar 

  • Carroll RC, Beattie EC, Xia H, Luscher C, Altschuler Y, Nicoll RA, Malenka RC, Zastrow M von (1999b) Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc Natl Acad Sci USA 96:14112–14117

    PubMed  CAS  Google Scholar 

  • Chambers JJ, Gouda H, Young DM, Kuntz ID, England PM (2004) Photochemically knocking out glutamate receptors in vivo. J Am Chem Soc 126:13886–13887

    PubMed  CAS  Google Scholar 

  • Chen HJ, Rojas-Soto M, Oguni A, Kennedy MB (1998) A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20:895–904

    PubMed  CAS  Google Scholar 

  • Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA (2000) Stargazing regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408:936–943

    PubMed  CAS  Google Scholar 

  • Choquet D, Triller A (2003) The role of receptor diffusion in the organization of the postsynaptic membrane. Nat Rev Neurosci 4:251–265

    PubMed  CAS  Google Scholar 

  • Chung HJ, Xia J, Scannevin RH, Zhang X, Huganir RL (2000) Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci 20:7258–7267

    PubMed  CAS  Google Scholar 

  • Chung HJ, Steinberg JP, Huganir RL, Linden DJ (2003) Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science 300:1751–1755

    PubMed  CAS  Google Scholar 

  • Clem RL, Barth A (2006) Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron 49:663–670

    PubMed  CAS  Google Scholar 

  • Coleman SK, Cai C, Mottershead DG, Haapalahti JP, Keinanen K (2003) Surface expression of GluR-D AMPA receptor is dependent on an interaction between its C-terminal domain and a 4.1 protein. J Neurosci 23:798–806

    PubMed  CAS  Google Scholar 

  • Colledge M, Dean RA, Scott GK, Langeberg LK, Huganir RL, Scott JD (2000) Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex. Neuron 27:107–119

    PubMed  CAS  Google Scholar 

  • Collingridge GL, Isaac JT, Wang YT (2004) Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 5:952–962

    PubMed  CAS  Google Scholar 

  • Cooney JR, Hurlburt JL, Selig DK, Harris KM, Fiala JC (2002) Endosomal compartments serve multiple hippocampal dendritic spines from a widespread rather than a local store of recycling membrane. J Neurosci 22:2215–2224

    PubMed  CAS  Google Scholar 

  • Cottrell JR, Borok E, Horvath TL, Nedivi E (2004) CPG2: a brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors. Neuron 44:677–690

    PubMed  CAS  Google Scholar 

  • Dahan M, Levi S, Luccardini C, Rostaing P, Riveau B, Triller A (2003) Diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Science 302:442–445

    PubMed  CAS  Google Scholar 

  • Daw MI, Chittajallu R, Bortolotto ZA, Dev KK, Duprat F, Henley JM, Collingridge GL, Isaac JT (2000) PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses. Neuron 28:873–886

    PubMed  CAS  Google Scholar 

  • DeSouza S, Fu J, States BA, Ziff EB (2002) Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters. J Neurosci 22:3493–3503

    PubMed  CAS  Google Scholar 

  • Dev KK, Nishimune A, Henley JM, Nakanishi S (1999) The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology 38:635–644

    PubMed  CAS  Google Scholar 

  • Dong H, RJ OB, Fung ET, Lanahan AA, Worley PF, Huganir RL (1997) GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386:279–284

    PubMed  CAS  Google Scholar 

  • Ehlers MD (2000) Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting. Neuron 28:511–525

    PubMed  CAS  Google Scholar 

  • Ehrlich I, Malinow R (2004) Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci 24:916–927

    PubMed  CAS  Google Scholar 

  • El-Husseini AE, Schnell E, Chetkovich DM, Nicoll RA, Bredt DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 290:1364–1368

    PubMed  CAS  Google Scholar 

  • El-Husseini Ael D, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O, Gauthier-Campbell C, Aguilera-Moreno A, Nicoll RA, Bredt DS (2002) Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108:849–863

    Google Scholar 

  • Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R (2003) PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat Neurosci 6:136–143

    PubMed  CAS  Google Scholar 

  • Fong DK, Rao A, Crump FT, Craig AM (2002) Rapid synaptic remodeling by protein kinase C: reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II. J Neurosci 22:2153–2164

    PubMed  CAS  Google Scholar 

  • Fukata Y, Tzingounis AV, Trinidad JC, Fukata M, Burlingame AL, Nicoll RA, Bredt DS (2005) Molecular constituents of neuronal AMPA receptors. J Cell Biol 169:399–404

    PubMed  CAS  Google Scholar 

  • Gardner SM, Takamiya K, Xia J, Suh JG, Johnson R, Yu S, Huganir RL (2005) Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 45:903–915

    PubMed  CAS  Google Scholar 

  • Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JA (2006) Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane. EMBO J 25:1623–1634

    PubMed  CAS  Google Scholar 

  • Gerrow K, Romorini S, Nabi SM, Colicos MA, Sala C, El-Husseini A (2006) A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49:547–562

    PubMed  CAS  Google Scholar 

  • Greger IH, Khatri L, Ziff EB (2002) RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum. Neuron 34:759–772

    PubMed  CAS  Google Scholar 

  • Groc L, Heine M, Cognet L, Brickley K, Stephenson FA, Lounis B, Choquet D (2004) Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors. Nat Neurosci 7:695–696

    PubMed  CAS  Google Scholar 

  • Guillaud L, Setou M, Hirokawa N (2003) KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons. J Neurosci 23:131–140

    PubMed  CAS  Google Scholar 

  • Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R (2000) Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 287:2262–2267

    PubMed  CAS  Google Scholar 

  • Heynen AJ, Quinlan EM, Bae DC, Bear MF (2000) Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo. Neuron 28:527–536

    PubMed  CAS  Google Scholar 

  • Hirokawa N, Takemura R (2004) Molecular motors in neuronal development, intracellular transport and diseases. Curr Opin Neurobiol 14:564–573

    PubMed  CAS  Google Scholar 

  • Hollman M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108

    Google Scholar 

  • Hoover KB, Bryant PJ (2000) The genetics of the protein 4.1 family: organizers of the membrane and cytoskeleton. Curr Opin Cell Biol 12:229–234

    PubMed  CAS  Google Scholar 

  • Howarth M, Takao K, Hayashi Y, Ting AY (2005) Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc Natl Acad Sci USA 102:7583–7588

    PubMed  CAS  Google Scholar 

  • Huh KH, Wenthold RJ (1999) Turnover analysis of glutamate receptors identifies a rapidly degraded pool of the N-methyl-D-aspartate receptor subunit, NR1, in cultured cerebellar granule cells. J Biol Chem 274:151–157

    PubMed  CAS  Google Scholar 

  • Jensen V, Kaiser KM, Borchardt T, Adelmann G, Rozov A, Burnashev N, Brix C, Frotscher M, Andersen P, Hvalby O, Sakmann B, Seeburg PH, Sprengel R (2003) A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A. J Physiol (Lond) 553:843–856

    CAS  Google Scholar 

  • Jia Z, Agopyan N, Miu P, Xiong Z, Henderson J, Gerlai R, Taverna FA, Velumian A, MacDonald J, Carlen P, Abramow-Newerly W, Roder J (1996) Enhanced LTP in mice deficient in the AMPA receptor GluR2. Neuron 17:945–956

    PubMed  CAS  Google Scholar 

  • Ju W, Morishita W, Tsui J, Gaietta G, Deerinck TJ, Adams SR, Garner CC, Tsien RY, Ellisman MH, Malenka RC (2004) Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors. Nat Neurosci 7:244–253

    PubMed  CAS  Google Scholar 

  • Kawasaki H, Springett GM, Toki S, Canales JJ, Harlan P, Blumenstiel JP, Chen EJ, Bany IA, Mochizuki N, Ashbacher A, Matsuda M, Housman DE, Graybiel AM (1998) A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci USA 95:13278–13283

    PubMed  CAS  Google Scholar 

  • Kennedy MJ, Ehlers MD (2006) Organelles and trafficking machinery for postsynaptic plasticity. Annu Rev Neurosci 29:325–362

    PubMed  CAS  Google Scholar 

  • Kim JH, Liao D, Lau LF, Huganir RL (1998) SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20:683–691

    PubMed  CAS  Google Scholar 

  • Kim CH, Chung HJ, Lee HK, Huganir RL (2001) Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression. Proc Natl Acad Sci USA 98:11725–11730

    PubMed  CAS  Google Scholar 

  • Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ, Kim E (2003) Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting. J Neurosci 23:1667–1677

    PubMed  CAS  Google Scholar 

  • Kopec CD, Li B, Wei W, Boehm J, Malinow R (2006) Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. J Neurosci 26:2000–2009

    PubMed  CAS  Google Scholar 

  • Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushiya E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M, et al (1992) Molecular diversity of the NMDA receptor channel. Nature 358:36–41

    PubMed  CAS  Google Scholar 

  • Lee HK, Takamiya K, Han JS, Man H, Kim CH, Rumbaugh G, Yu S, Ding L, He C, Petralia RS, Wenthold RJ, Gallagher M, Huganir RL (2003) Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112:631–643

    PubMed  CAS  Google Scholar 

  • Lee SH, Liu L, Wang YT, Sheng M (2002) Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 36:661–674

    PubMed  CAS  Google Scholar 

  • Lee SH, Simonetta A, Sheng M (2004) Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron 43:221–236

    PubMed  CAS  Google Scholar 

  • Lin JW, Ju W, Foster K, Lee SH, Ahmadian G, Wyszynski M, Wang YT, Sheng M (2000) Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nat Neurosci 3:1282–1290

    PubMed  CAS  Google Scholar 

  • Lise MF, Wong TP, Trinh A, Hines RM, Liu L, Kang R, Hines DJ, Lu J, Goldenring JR, Wang YT, El-Husseini A (2006) Involvement of myosin Vb in glutamate receptor trafficking. J Biol Chem 281:3669–3678

    PubMed  CAS  Google Scholar 

  • Lisman J (2003) Long-term potentiation: outstanding questions and attempted synthesis. Philos Trans R Soc Lond Biol 358:829–842

    PubMed  CAS  Google Scholar 

  • Lisman J, Schulman H, Cline H (2002) The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 3:175–190

    PubMed  CAS  Google Scholar 

  • Lledo PM, Zhang X, Sudhof TC, Malenka RC, Nicoll RA (1998) Postsynaptic membrane fusion and long-term potentiation. Science 279:399–403

    PubMed  CAS  Google Scholar 

  • Lu W, Man H, Ju W, Trimble WS, MacDonald JF, Wang YT (2001) Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 29:243–254

    PubMed  CAS  Google Scholar 

  • Luscher C, Xia H, Beattie EC, Carroll RC, Zastrow M von, Malenka RC, Nicoll RA (1999) Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24:649–658

    PubMed  CAS  Google Scholar 

  • Luthi A, Chittajallu R, Duprat F, Palmer MJ, Benke TA, Kidd FL, Henley JM, Isaac JT, Collingridge GL (1999) Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 24:389–399

    PubMed  CAS  Google Scholar 

  • Mack V, Burnashev N, Kaiser KM, Rozov A, Jensen V, Hvalby O, Seeburg PH, Sakmann B, Sprengel R (2001) Conditional restoration of hippocampal synaptic potentiation in GluR-A-deficient mice. Science 292:2501–2504

    PubMed  CAS  Google Scholar 

  • Malenka RC, Nicoll RA (1999) Long-term potentiation—a decade of progress? Science 285:1870–1874

    PubMed  CAS  Google Scholar 

  • Malinow R (2003) AMPA receptor trafficking and long-term potentiation. Philos Trans R Soc Lond Biol 358:707–714

    PubMed  CAS  Google Scholar 

  • Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126

    PubMed  CAS  Google Scholar 

  • Mammen AL, Kameyama K, Roche KW, Huganir RL (1997) Phosphorylation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit by calcium/calmodulin-dependent kinase II. J Biol Chem 272:32528–32533

    PubMed  CAS  Google Scholar 

  • Man HY, Lin JW, Ju WH, Ahmadian G, Liu L, Becker LE, Sheng M, Wang YT (2000) Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron 25:649–662

    PubMed  CAS  Google Scholar 

  • Man HY, Wang Q, Lu WY, Ju W, Ahmadian G, Liu L, D’Souza S, Wong TP, Taghibiglou C, Lu J, Becker LE, Pei L, Liu F, Wymann MP, MacDonald JF, Wang YT (2003) Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons. Neuron 38:611–624

    PubMed  CAS  Google Scholar 

  • Maren S, Tocco G, Standley S, Baudry M, Thompson RF (1993) Postsynaptic factors in the expression of long-term potentiation (LTP): increased glutamate receptor binding following LTP induction in vivo. Proc Natl Acad Sci USA 90:9654–9658

    PubMed  CAS  Google Scholar 

  • Matsuda S, Mikawa S, Hirai H (1999) Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein. J Neurochem 73:1765–1768

    PubMed  CAS  Google Scholar 

  • Mayer ML, Armstrong N (2004) Structure and function of glutamate receptor ion channels. Annu Rev Physiol 66:161–181

    PubMed  CAS  Google Scholar 

  • McIlhinney RA, Le Bourdelles B, Molnar E, Tricaud N, Streit P, Whiting PJ (1998) Assembly intracellular targeting and cell surface expression of the human N-methyl-D-aspartate receptor subunits NR1a and NR2A in transfected cells. Neuropharmacology 37:1355–1367

    PubMed  CAS  Google Scholar 

  • Meguro H, Mori H, Araki K, Kushiya E, Kutsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M (1992) Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 357:70–74

    PubMed  CAS  Google Scholar 

  • Meier J, Vannier C, Sergé A, Triller A, Choquet D (2001) Fast and reversible trapping of surface glycine receptors by gephyrin. Nat Neurosci 4:253–260

    PubMed  CAS  Google Scholar 

  • Meng Y, Zhang Y, Jia Z (2003) Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3. Neuron 39:163–176

    PubMed  CAS  Google Scholar 

  • Metzler M, Li B, Gan L, Georgiou J, Gutekunst CA, Wang Y, Torre E, Devon RS, Oh R, Legendre-Guillemin V, Rich M, Alvarez C, Gertsenstein M, McPherson PS, Nagy A, Wang YT, Roder JC, Raymond LA, Hayden MR (2003) Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. EMBO J 22:3254–3266

    PubMed  CAS  Google Scholar 

  • Miesenbock G, De Angelis DA, Rothman JE (1998) Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394:192–195

    PubMed  CAS  Google Scholar 

  • Mok H, Shin H, Kim S, Lee JR, Yoon J, Kim E (2002) Association of the kinesin superfamily motor protein KIF1Balpha with postsynaptic density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule PSD-95/discs large/zona occludens-1 proteins. J Neurosci 22:5253–5258

    PubMed  CAS  Google Scholar 

  • Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (1992) Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221

    PubMed  CAS  Google Scholar 

  • Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529–540

    PubMed  CAS  Google Scholar 

  • Mu Y, Otsuka T, Horton AC, Scott DB, Ehlers MD (2003) Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors. Neuron 40:581–594

    PubMed  CAS  Google Scholar 

  • Nakada C, Ritchie K, Oba Y, Nakamura M, Hotta Y, Iino R, Kasai RS, Yamaguchi K, Fujiwara T, Kusumi A (2003) Accumulation of anchored proteins forms membrane diffusion barriers during neuronal polarization. Nat Cell Biol 5:626–632

    PubMed  CAS  Google Scholar 

  • Nicoll RA, Tomita S, Bredt DS (2006) Auxiliary subunits assist AMPA-type glutamate receptors. Science 311:1253–1256

    PubMed  CAS  Google Scholar 

  • Nishimune A, Isaac JT, Molnar E, Noel J, Nash SR, Tagaya M, Collingridge GL, Nakanishi S, Henley JM (1998) NSF binding to GluR2 regulates synaptic transmission. Neuron 21:87–97

    PubMed  CAS  Google Scholar 

  • Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL, Henley JM (1999) Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron 23:365–376

    PubMed  CAS  Google Scholar 

  • Nong Y, Huang YQ, Ju W, Kalia LV, Ahmadian G, Wang YT, Salter MW (2003) Glycine binding primes NMDA receptor internalization. Nature 422:302–307

    PubMed  CAS  Google Scholar 

  • Nong Y, Huang YQ, Salter MW (2004) NMDA receptors are movin’ in. Curr Opin Neurobiol 14:353–361

    PubMed  CAS  Google Scholar 

  • Oh MC, Derkach VA, Guire ES, Soderling TR (2006) Extrasynaptic membrane trafficking regulated by GluR1 serine 845 phosphorylation primes AMPA receptors for long-term potentiation. J Biol Chem 281:752–758

    PubMed  CAS  Google Scholar 

  • Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD (2004) Recycling endosomes supply AMPA receptors for LTP. Science 305:1972–1975

    PubMed  CAS  Google Scholar 

  • Passafaro M, Piech V, Sheng M (2001) Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat Neurosci 4:917–926

    PubMed  CAS  Google Scholar 

  • Perestenko PV, Henley JM (2003) Characterisation of the intracellular transport of GluR1 and GluR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunits in hippocampal neurons. J Biol Chem 278:43525–43532

    PubMed  CAS  Google Scholar 

  • Perez JL, Khatri L, Chang C, Srivastava S, Osten P, Ziff EB (2001) PICK1 targets activated protein kinase C alpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci 21:5417–5428

    PubMed  CAS  Google Scholar 

  • Perez-Otano I, Ehlers MD (2005) Homeostatic plasticity and NMDA receptor trafficking. Trends Neurosci 28:229–238

    PubMed  CAS  Google Scholar 

  • Petralia RS, Wang YX, Wenthold RJ (2003) Internalization at glutamatergic synapses during development. Eur J Neurosci 18:3207–3217

    PubMed  Google Scholar 

  • Petralia RS, Sans N, Wang YX, Wenthold RJ (2005) Ontogeny of postsynaptic density proteins at glutamatergic synapses. Mol Cell Neurosci 29:436–452

    PubMed  CAS  Google Scholar 

  • Pickard L, Noel J, Duckworth JK, Fitzjohn SM, Henley JM, Collingridge GL, Molnar E (2001) Transient synaptic activation of NMDA receptors leads to the insertion of native AMPA receptors at hippocampal neuronal plasma membranes. Neuropharmacology 41:700–713

    PubMed  CAS  Google Scholar 

  • Prybylowski K, Fu Z, Losi G, Hawkins LM, Luo J, Chang K, Wenthold RJ, Vicini S (2002) Relationship between availability of NMDA receptor subunits and their expression at the synapse. J Neurosci 22:8902–8910

    PubMed  CAS  Google Scholar 

  • Prybylowski K, Chang K, Sans N, Kan L, Vicini S, Wenthold RJ (2005) The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron 47:845–857

    PubMed  CAS  Google Scholar 

  • Racz B, Blanpied TA, Ehlers MD, Weinberg RJ (2004) Lateral organization of endocytic machinery in dendritic spines. Nat Neurosci 7:917–918

    PubMed  CAS  Google Scholar 

  • Richards DA, De Paola V, Caroni P, Gahwiler BH, McKinney RA (2004) AMPA-receptor activation regulates the diffusion of a membrane marker in parallel with dendritic spine motility in the mouse hippocampus. J Physiol (Lond) 558:503–512

    CAS  Google Scholar 

  • Roche KW, O’Brien RJ, Mammen AL, Bernhardt J, Huganir RL (1996) Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16:1179–1188

    PubMed  CAS  Google Scholar 

  • Roche KW, Standley S, McCallum J, Dune Ly C, Ehlers MD, Wenthold RJ (2001) Molecular determinants of NMDA receptor internalization. Nat Neurosci 4:794–802

    PubMed  CAS  Google Scholar 

  • Rouach N, Byrd K, Petralia RS, Elias GM, Adesnik H, Tomita S, Karimzadegan S, Kealey C, Bredt DS, Nicoll RA (2005) TARP gamma-8 controls hippocampal AMPA receptor number, distribution and synaptic plasticity. Nat Neurosci 8:1525–1533

    PubMed  CAS  Google Scholar 

  • Rubio ME, Wenthold RJ (1999) Calnexin and the immunoglobulin binding protein (BiP) coimmunoprecipitate with AMPA receptors. J Neurochem 73:942–948

    PubMed  CAS  Google Scholar 

  • Rumpel S, LeDoux J, Zador A, Malinow R (2005) Postsynaptic receptor trafficking underlying a form of associative learning. Science 308:83–88

    PubMed  CAS  Google Scholar 

  • Sans N, Racca C, Petralia RS, Wang YX, McCallum J, Wenthold RJ (2001) Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway. J Neurosci 21:7506–7516

    PubMed  CAS  Google Scholar 

  • Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (2003) NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nat Cell Biol 5:520–530

    PubMed  CAS  Google Scholar 

  • Sans N, Wang PY, Du Q, Petralia RS, Wang YX, Nakka S, Blumer JB, Macara IG, Wenthold RJ (2005) mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nat Cell Biol 7:1079–1090

    CAS  Google Scholar 

  • Sawada Y, Nakamura K, Doi K, Takeda K, Tobiume K, Saitoh M, Morita K, Komuro I, De Vos K, Sheetz M, Ichijo H (2001) Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase. J Cell Sci 114:1221–1227

    PubMed  CAS  Google Scholar 

  • Schnell E, Sizemore M, Karimzadegan S, Chen L, Bredt DS, Nicoll RA (2002) Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proc Natl Acad Sci USA 99:13902–13907

    PubMed  CAS  Google Scholar 

  • Schorge S, Colquhoun D (2003) Studies of NMDA receptor function and stoichiometry with truncated and tandem subunits. J Neurosci 23:1151–1158

    PubMed  CAS  Google Scholar 

  • Schulz TW, Nakagawa T, Licznerski P, Pawlak V, Kolleker A, Rozov A, Kim J, Dittgen T, Kohr G, Sheng M, Seeburg PH, Osten P (2004) Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL. J Neurosci 24:8584–8594

    PubMed  CAS  Google Scholar 

  • Scott DB, Blanpied TA, Swanson GT, Zhang C, Ehlers MD (2001) An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J Neurosci 21:3063–3072

    PubMed  CAS  Google Scholar 

  • Sekine-Aizawa Y, Huganir RL (2004) Imaging of receptor trafficking by using alpha-bungarotoxin-binding-site-tagged receptors. Proc Natl Acad Sci USA 101:17114–17119

    PubMed  CAS  Google Scholar 

  • Sergé A, Fourgeaud L, Hémar A, Choquet D (2002) Receptor activation and homer differentially control the lateral mobility of mGluR5 in the neuronal membrane. J Neuroscience 22:3910–3920

    Google Scholar 

  • Setou M, Nakagawa T, Seog DH, Hirokawa N (2000) Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288:1796–1802

    PubMed  CAS  Google Scholar 

  • Setou M, Seog DH, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N (2002) Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites. Nature 417:83–87

    PubMed  CAS  Google Scholar 

  • Shen L, Liang F, Walensky LD, Huganir RL (2000) Regulation of AMPA receptor GluR1 subunit surface expression by a 4.1N-linked actin cytoskeletal association. J Neurosci 20:7932–7940

    PubMed  CAS  Google Scholar 

  • Sheng M, Kim MJ (2002) Postsynaptic signaling and plasticity mechanisms. Science 298:776–780

    PubMed  CAS  Google Scholar 

  • Sheng M, Cummings J, Roldan L, Jan Y, Jan L (1994) Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368:144–147

    PubMed  CAS  Google Scholar 

  • Shi S, Hayashi Y, Esteban JA, Malinow R (2001) Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105:331–343

    PubMed  CAS  Google Scholar 

  • Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J, Streuli M, Weinberg RJ, Sheng M, Kim E (2003) Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. J Biol Chem 278:11393–11401

    PubMed  CAS  Google Scholar 

  • Snyder EM, Philpot BD, Huber KM, Dong X, Fallon JR, Bear MF (2001) Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat Neurosci 4:1079–1085

    PubMed  CAS  Google Scholar 

  • Sommer B, Kohler M, Sprengel R, Seeburg PH (1991) RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67:11–19

    PubMed  CAS  Google Scholar 

  • Song I, Huganir RL (2002) Regulation of AMPA receptors during synaptic plasticity. Trends Neurosci 25:578–588

    PubMed  CAS  Google Scholar 

  • Song I, Kamboj S, Xia J, Dong H, Liao D, Huganir RL (1998) Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21:393–400

    PubMed  CAS  Google Scholar 

  • Spacek J, Harris KM (1997) Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J Neurosci 17:190–203

    PubMed  CAS  Google Scholar 

  • Srivastava S, Osten P, Vilim FS, Khatri L, Inman G, States B, Daly C, DeSouza S, Abagyan R, Valtschanoff JG, Weinberg RJ, Ziff EB (1998) Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 21:581–591

    PubMed  CAS  Google Scholar 

  • Standley S, Roche KW, McCallum J, Sans N, Wenthold RJ (2000) PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants. Neuron 28:887–898

    PubMed  CAS  Google Scholar 

  • Sweatt JD (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10

    PubMed  CAS  Google Scholar 

  • Takahashi T, Svoboda K, Malinow R (2003) Experience strengthening transmission by driving AMPA receptors into synapses. Science 299:1585–1588

    PubMed  CAS  Google Scholar 

  • Tardin C, Cognet L, Bats C, Lounis B, Choquet D (2003) Direct imaging of lateral movements of AMPA receptors inside synapses. EMBO J 22:4656–4665

    PubMed  CAS  Google Scholar 

  • Terashima A, Cotton L, Dev KK, Meyer G, Zaman S, Duprat F, Henley JM, Collingridge GL, Isaac JT (2004) Regulation of synaptic strength and AMPA receptor subunit composition by PICK1. J Neurosci 24:5381–5390

    PubMed  CAS  Google Scholar 

  • Tomita S, Chen L, Kawasaki Y, Petralia RS, Wenthold RJ, Nicoll RA, Bredt DS (2003) Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins. J Cell Biol 161:805–816

    PubMed  CAS  Google Scholar 

  • Tomita S, Fukata M, Nicoll RA, Bredt DS (2004) Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses. Science 303:1508–1511

    PubMed  CAS  Google Scholar 

  • Tomita S, Stein V, Stocker TJ, Nicoll RA, Bredt DS (2005) Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs. Neuron 45:269–277

    PubMed  CAS  Google Scholar 

  • Toni N, Buchs PA, Nikonenko I, Povilaitite P, Parisi L, Muller D (2001) Remodeling of synaptic membranes after induction of long-term potentiation. J Neurosci 21:6245–6251

    PubMed  CAS  Google Scholar 

  • Tovar KR, Westbrook GL (2002) Mobile NMDA receptors at hippocampal synapses. Neuron 34:255–264

    PubMed  CAS  Google Scholar 

  • Vandenberghe W, Nicoll RA, Bredt DS (2005) Interaction with the unfolded protein response reveals a role for stargazin in biosynthetic AMPA receptor transport. J Neurosci 25:1095–1102

    PubMed  CAS  Google Scholar 

  • Wang YT, Linden DJ (2000) Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25:635–647

    PubMed  CAS  Google Scholar 

  • Washbourne P, Bennett JE, McAllister AK (2002) Rapid recruitment of NMDA receptor transport packets to nascent synapses. Nat Neurosci 5:751–759

    PubMed  CAS  Google Scholar 

  • Washbourne P, Liu XB, Jones EG, McAllister AK (2004) Cycling of NMDA receptors during trafficking in neurons before synapse formation. J Neurosci 24:8253–8264

    PubMed  CAS  Google Scholar 

  • Wenthold RJ, Petralia RS, Blahos J II, Niedzielski AS (1996) Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci 16:1982–1989

    PubMed  CAS  Google Scholar 

  • Wenthold RJ, Sans N, Standley S, Prybylowski K, Petralia RS (2003a) Early events in the trafficking of N-methyl-D-aspartate (NMDA) receptors. Biochem Soc Trans 31:885–888

    PubMed  CAS  Google Scholar 

  • Wenthold RJ, Prybylowski K, Standley S, Sans N, Petralia RS (2003b) Trafficking of NMDA receptors. Annu Rev Pharmacol Toxicol 43:335–358

    PubMed  CAS  Google Scholar 

  • Winckler B, Forscher P, Mellman I (1999) A diffusion barrier maintains distribution of membrane proteins in polarized neurons. Nature 397:698–701

    PubMed  CAS  Google Scholar 

  • Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pages C, Streuli M, Weinberg RJ, Sheng M (2002) Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron 34:39–52

    PubMed  CAS  Google Scholar 

  • Xia H, Hornby ZD, Malenka RC (2001) An ER retention signal explains differences in surface expression of NMDA and AMPA receptor subunits. Neuropharmacology 41:714–723

    PubMed  CAS  Google Scholar 

  • Xia J, Zhang X, Staudinger J, Huganir RL (1999) Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22:179–187

    PubMed  CAS  Google Scholar 

  • Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ (2000) Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron 28:499–510

    PubMed  CAS  Google Scholar 

  • Yasuda H, Barth AL, Stellwagen D, Malenka RC (2003) A developmental switch in the signaling cascades for LTP induction. Nat Neurosci 6:15–16

    PubMed  CAS  Google Scholar 

  • Young SH, Poo MM (1983) Rapid lateral diffusion of extrajunctional acetylcholine receptors in the developing muscle membrane of Xenopus tadpole. J Neurosci 3:225–231

    PubMed  CAS  Google Scholar 

  • Zamanillo D, Sprengel R, Hvalby O, Jensen V, Burnashev N, Rozov A, Kaiser KM, Koster HJ, Borchardt T, Worley P, Lubke J, Frotscher M, Kelly PH, Sommer B, Andersen P, Seeburg PH, Sakmann B (1999) Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284:1805–1811

    PubMed  CAS  Google Scholar 

  • Zhou Q, Xiao M, Nicoll RA (2001) Contribution of cytoskeleton to the internalization of AMPA receptors. Proc Natl Acad Sci USA 98:1261–1266

    PubMed  CAS  Google Scholar 

  • Zhu JJ, Esteban JA, Hayashi Y, Malinow R (2000) Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity. Nat Neurosci 3:1098–1106

    PubMed  CAS  Google Scholar 

  • Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R (2002) Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110:443–455

    PubMed  CAS  Google Scholar 

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  1. UMR 5091 CNRS-Université de Bordeaux 2 Physiologie Cellulaire de la Synapse, Institut François Magendie, Rue Camille Saint Saëns, 33077, Bordeaux Cédex, France

    Laurent Groc & Daniel Choquet

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Groc, L., Choquet, D. AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse. Cell Tissue Res 326, 423–438 (2006). https://doi.org/10.1007/s00441-006-0254-9

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