Phosphorylation of AMPA receptors: mechanisms and synaptic plasticity.
The ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is densely distributed in the mammalian brain and is primarily involved in mediating fast excitatory synaptic transmission. Recent studies in both heterologous expression systems and cultured neurons have shown that the AMPA receptor can be phosphorylated on their subunits (GluR1, GluR2, and GluR4). All phosphorylation sites reside at serine, threonine, or tyrosine on the intracellular C-terminal domain. Several key protein kinases, such as protein kinase A, protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and tyrosine kinases (Trks; receptor or nonreceptor family Trks) are involved in the site-specific regulation of the AMPA receptor phosphorylation. Other glutamate receptors (N-methyl-d-aspartate receptors and metabotropic glutamate receptors) also regulate AMPA receptors through a protein phosphorylation mechanism. Emerging evidence shows that as a rapid and short-term mechanism, the dynamic protein phosphorylation directly modulates the electrophysiological, morphological (externalization and internalization trafficking and clustering), and biochemical (synthesis and subunit composition) properties of the AMPA receptor, as well as protein-protein interactions between the AMPA receptor subunits and various intracellular interacting proteins. These modulations underlie the major molecular mechanisms that ultimately affect many forms of synaptic plasticity.
Wang
John Q
JQ
Department of Basic Medical Science, University of Missouri-Kansas City, School of Medicine, USA. wangjq@umkc.edu
Arora
Anish
A
Yang
Lu
L
Parelkar
Nikhil K
NK
Zhang
Guochi
G
Liu
Xianyu
X
Choe
Eun Sang
ES
Mao
Limin
L
D000595:Amino Acid Sequence; D000818:Animals; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D009435:Synaptic Transmission
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors