Driving AMPA receptors into synapses by LTP and CaMKII: Requirement for GluR1 and PDZ domain interaction

Science

Volumn 287, Issue 5461, 2000, Pages 2262-2267

  Hayashi, Yasunori ^a   Shi, Song Hai ^a   Esteban, José A ^a   Piccini, Antonella ^a   Poncer, Jean Christophe ^a   Malinow, Roberto ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

AMPA RECEPTOR; PROTEIN KINASE (CALCIUM,CALMODULIN) II;

ANIMAL CELL; ARTICLE; ENZYME ACTIVITY; HIPPOCAMPUS; LONG TERM POTENTIATION; MUTATION; NERVE CELL PLASTICITY; NONHUMAN; PHOSPHORYLATION; PRIORITY JOURNAL; RAT; SYNAPSE;

ANIMALS; CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASE; CATALYTIC DOMAIN; CELL LINE; HIPPOCAMPUS; HUMANS; LONG-TERM POTENTIATION; MEMBRANE POTENTIALS; MUTATION; ORGAN CULTURE TECHNIQUES; PATCH-CLAMP TECHNIQUES; PHOSPHORYLATION; PROTEIN STRUCTURE, TERTIARY; PROTEINS; PYRAMIDAL CELLS; RATS; RECEPTORS, AMPA; RECOMBINANT FUSION PROTEINS; SYNAPSES; SYNAPTIC TRANSMISSION;

ANIMALIA; HIPPOCAMPUS HIPPOCAMPUS;

EID: 0034708587     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.287.5461.2262     Document Type: Article

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39. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr. X indicates any residue.
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42. 831, possibly by preventing a protein-protein interaction mediated by the hydroxyl group of Ser. The marked synaptic potentiation seen in cells expressing GluR1(S831A)-GFP-IRES-tCaMKII supports this view.
43. 887 by CaMKII is not likely because, in the case of GluR1, phosphorylation stimulated by either neuronal activity or CaMKII occurs exclusively on the Ser residue in both endogenous and recombinant protein, but not on the Thr residue [C. Blackstone et al., J. Neurosci. 14, 7585 (1994); A. Barria, thesis, Votlum Institute, Portland, OR (1998)].
44. 887 by CaMKII is not likely because, in the case of GluR1, phosphorylation stimulated by either neuronal activity or CaMKII occurs exclusively on the Ser residue in both endogenous and recombinant protein, but not on the Thr residue [C. Blackstone et al., J. Neurosci. 14, 7585 (1994); A. Barria, thesis, Votlum Institute, Portland, OR (1998)].
45. The depression by GluR1(T887A)-GFP of transmission may be explained in the following manner. Normally, there is a pool of GluR1-containing AMPA-Rs outside the synapse. Upon activation of CaMKII-dependent plasticity, these receptors are incorporated into a delivery pathway in which PDZ proteins play a critical role. This delivery process may contain elements used in a separate, constitutive delivery process; such a process appears to act on AMPA-Rs containing GluR2 and requires N-ethylmaleimide-sensitive fusion protein (NSF). The mutant receptor appears to be recruited, upon CaMKII activation or LTP, into an interaction site where it can block this constitutive process; the time-course of its effects on transmission is similar to the effect of peptides that block the interaction between GluR2 and NSF [A. Nishimune et al., Neuron 21, 87 (1998); P. Osten et al., Neuron 21, 99 (1998); I. Song et al., Neuron 21, 393 (1998); J. Noel et al., Neuron 23, 365 (1999)].
46. The depression by GluR1(T887A)-GFP of transmission may be explained in the following manner. Normally, there is a pool of GluR1-containing AMPA-Rs outside the synapse. Upon activation of CaMKII- dependent plasticity, these receptors are incorporated into a delivery pathway in which PDZ proteins play a critical role. This delivery process may contain elements used in a separate, constitutive delivery process; such a process appears to act on AMPA-Rs containing GluR2 and requires N-ethylmaleimide- sensitive fusion protein (NSF). The mutant receptor appears to be recruited, upon CaMKII activation or LTP, into an interaction site where it can block this constitutive process; the time-course of its effects on transmission is similar to the effect of peptides that block the interaction between GluR2 and NSF [A. Nishimune et al., Neuron 21, 87 (1998); P. Osten et al., Neuron 21, 99 (1998); I. Song et al., Neuron 21, 393 (1998); J. Noel et al., Neuron 23, 365 (1999)].
47. The depression by GluR1(T887A)-GFP of transmission may be explained in the following manner. Normally, there is a pool of GluR1-containing AMPA-Rs outside the synapse. Upon activation of CaMKII- dependent plasticity, these receptors are incorporated into a delivery pathway in which PDZ proteins play a critical role. This delivery process may contain elements used in a separate, constitutive delivery process; such a process appears to act on AMPA-Rs containing GluR2 and requires N-ethylmaleimide- sensitive fusion protein (NSF). The mutant receptor appears to be recruited, upon CaMKII activation or LTP, into an interaction site where it can block this constitutive process; the time-course of its effects on transmission is similar to the effect of peptides that block the interaction between GluR2 and NSF [A. Nishimune et al., Neuron 21, 87 (1998); P. Osten et al., Neuron 21, 99 (1998); I. Song et al., Neuron 21, 393 (1998); J. Noel et al., Neuron 23, 365 (1999)].
48. The depression by GluR1(T887A)-GFP of transmission may be explained in the following manner. Normally, there is a pool of GluR1-containing AMPA-Rs outside the synapse. Upon activation of CaMKII- dependent plasticity, these receptors are incorporated into a delivery pathway in which PDZ proteins play a critical role. This delivery process may contain elements used in a separate, constitutive delivery process; such a process appears to act on AMPA-Rs containing GluR2 and requires N-ethylmaleimide- sensitive fusion protein (NSF). The mutant receptor appears to be recruited, upon CaMKII activation or LTP, into an interaction site where it can block this constitutive process; the time-course of its effects on transmission is similar to the effect of peptides that block the interaction between GluR2 and NSF [A. Nishimune et al., Neuron 21, 87 (1998); P. Osten et al., Neuron 21, 99 (1998); I. Song et al., Neuron 21, 393 (1998); J. Noel et al., Neuron 23, 365 (1999)].
49. Supplemental material is available at www. sciencemag.org/feature/data/1046986.shl
50. We thank C. Sano for help in DNA construction, N. Dawkins-Pisani for technical assistance, and H. Schulman, M. Hollmann, and S. F. Heineman for cDNA clones. Y.H. was supported by Japan Society for the Promotion of Science and Uehara Memorial Foundation, J.A.E. by Alzheimer Association and National Alliance for Research on Schizophrenia and Depression, and J.-C.P. by the Human Frontier Science Program Organization. This study was supported by NIH and the Mathers Foundation (to R.M).