Control of synaptic strength, a novel function of Akt.
Akt (also known as PKB), a serine/threonine kinase involved in diverse signal-transduction pathways, is highly expressed in the brain. Akt is known to have a strong antiapoptotic action and thereby to be critically involved in neuronal survival, but its potential role in the dynamic modulation of synaptic transmission is unknown. Here we report that Akt phosphorylates, both in vitro and in vivo, the type A gamma-aminobutyric acid receptor (GABA(A)R), the principal receptor mediating fast inhibitory synaptic transmission in the mammalian brain. Akt-mediated phosphorylation increases the number of GABA(A)Rs on the plasma membrane surface, thereby increasing the receptor-mediated synaptic transmission in neurons. These results identify the GABA(A)R as a novel substrate of Akt, thereby linking Akt to the regulation of synaptic strength. This work also provides evidence for the rapid regulation of neurotransmitter receptor numbers in the postsynaptic domain by direct receptor phosphorylation as an important means of producing synaptic plasticity.
Wang
Qinghua
Q
Programme in Brain and Behaviour Research, Research Institute of the Hospital for Sick Children, University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Ontario, Canada.
Liu
Lidong
L
Pei
Lin
L
Ju
William
W
Ahmadian
Gholamreza
G
Lu
Jie
J
Wang
Yushan
Y
Liu
Fang
F
Wang
Yu Tian
YT
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004594:Electrophysiology; D004789:Enzyme Activation; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D017553:Phosphorus Compounds; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011963:Receptors, GABA-A / Q000032:analysis / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014162:Transfection
D017553:Phosphorus Compounds; D011518:Proto-Oncogene Proteins; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D010768:Phosphoserine; C013196:phosphoryl chloride; D005982:Glutathione Transferase; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt