title: Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1.
abstract: Incorporation of GluR1-containing AMPA receptors into synapses is essential to several forms of neural plasticity, including long-term potentiation (LTP). Numerous signaling pathways that trigger this process have been identified, but the direct modifications of GluR1 that control its incorporation into synapses are unclear. Here, we show that phosphorylation of GluR1 by PKC at a highly conserved serine 818 residue is increased during LTP and critical for LTP expression. GluR1 is phosphorylated by PKC at this site in vitro and in vivo. In addition, acute phosphorylation at GluR1 S818 by PKC, as well as a phosphomimetic mutation, promotes GluR1 synaptic incorporation. Conversely, preventing GluR1 S818 phosphorylation reduces LTP and blocks PKC-driven synaptic incorporation of GluR1. We conclude that the phosphorylation of GluR1 S818 by PKC is a critical event in the plasticity-driven synaptic incorporation of AMPA receptors.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Jannic
authors.initials: J
authors.lastname: Boehm
authors.forename: Myoung-Goo
authors.initials: MG
authors.lastname: Kang
authors.forename: Richard C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Jose
authors.initials: J
authors.lastname: Esteban
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D006801:Humans; D017774:Long-Term Potentiation / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D011493:Protein Kinase C; D018091:Receptors, AMPA