Phosphorylation of ligand-gated ion channels: a possible mode of synaptic plasticity.
Most neurotransmitter receptors examined to date have been shown either to be regulated by protein phosphorylation or to contain consensus sequences for phosphorylation by protein kinases. Neurotransmitter receptors that mediate rapid synaptic transmission in the nervous system are the ligand-gated ion channels and include the nicotinic acetylcholine receptors of muscle and nerve and the excitatory and inhibitory amino acid receptors: the glutamate, GABAA, and glycine receptors. These receptors are multimeric proteins composed of homologous subunits which each span the membrane several times and contain a large intracellular loop that is a mosaic of consensus sites for protein phosphorylation. Recent evidence has suggested that extracellular signals released from the presynaptic neuron, such as neurotransmitters and neuropeptides as well as an extracellular matrix protein, regulate the phosphorylation of ligand-gated ion channels. The functional effects of phosphorylation are varied and include the regulation of receptor desensitization rate, subunit assembly, and receptor aggregation at the synapse. These results suggest that phosphorylation of neurotransmitter receptors represents a major mechanism in the regulation of their function and may play an important role in synaptic plasticity.
Swope
S L
SL
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Moss
S J
SJ
Blackstone
C D
CD
Huganir
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D013569:Synapses / Q000502:physiology*
D007473:Ion Channels; D008024:Ligands; D017981:Receptors, Neurotransmitter; D011494:Protein Kinases