Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1.
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.
Boehm
Jannic
J
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Kang
Myoung-Goo
MG
Johnson
Richard C
RC
Esteban
Jose
J
Huganir
Richard L
RL
Malinow
Roberto
R
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
D011493:Protein Kinase C; D018091:Receptors, AMPA