title: Rap2-JNK removes synaptic AMPA receptors during depotentiation.
abstract: The related small GTPases Ras and Rap1 are important for signaling synaptic AMPA receptor (-R) trafficking during long-term potentiation (LTP) and long-term depression (LTD), respectively. Rap2, which shares 60% identity to Rap1, is present at excitatory synapses, but its functional role is unknown. Here, we report that Rap2 activity, stimulated by NR2A-containing NMDA-R activation, depresses AMPA-R-mediated synaptic transmission via activation of JNK rather than Erk1/2 or p38 MAPK. Moreover, Rap2 controls synaptic removal of AMPA-Rs with long cytoplasmic termini during depotentiation. Thus, Rap2-JNK pathway, which opposes the action of the NR2A-containing NMDA-R-stimulated Ras-ERK1/2 signaling and complements the NR2B-containing NMDA-R-stimulated Rap1-p38 MAPK signaling, channels the specific signaling for depotentiating central synapses.
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Daniel
authors.initials: D
authors.lastname: Pak
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.forename: Stefanie G
authors.initials: SG
authors.lastname: McCormack
authors.forename: Myung J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Joel P
authors.initials: JP
authors.lastname: Baumgart
authors.forename: Vanisree
authors.initials: V
authors.lastname: Velamoor
authors.forename: Yves P
authors.initials: YP
authors.lastname: Auberson
authors.forename: Pavel
authors.initials: P
authors.lastname: Osten
authors.forename: Linda
authors.initials: L
authors.lastname: van Aelst
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: J Julius
authors.initials: JJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000145:classification / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008959:Models, Neurological; D016296:Mutagenesis / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D008274:Magnesium; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D011994:Recombinant Proteins; D014633:Valine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D020668:rap GTP-Binding Proteins; C056639:2-amino-5-phosphopentanoic acid; C104722:glutamate receptor ionotropic, AMPA 2