Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation.
Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently utilized for the analysis of the molecular mechanisms of memory formation. Extensive studies have demonstrated that various kinases and phosphatases regulate neuronal plasticity by phosphorylating and dephosphorylating proteins essential to the basic processes of adaptive changes in the CNS. These proteins include receptors, ion channels, synaptic vesicle proteins, and nuclear proteins. Multifunctional kinases (cAMP-dependent protein kinase, Ca2+/phospholipid-dependent protein kinase, and Ca2+/calmodulin-dependent protein kinases) and phosphatases (calcineurin, protein phosphatases 1, and 2A) that specifically modulate the phosphorylation status of neuronal-signaling proteins have been shown to be required for neuronal plasticity. In general, kinases are involved in upregulation of the activity of target substrates, and phosphatases downregulate them. Although this rule is applicable in most of the cases studied, there are also a number of exceptions. A variety of regulation mechanisms via phosphorylation and dephosphorylation mediated by multiple kinases and phosphatases are discussed.
Tokuda
M
M
Department of Physiology, Kagawa Medical University, Japan.
Hatase
O
O
D000818:Animals; D001921:Brain / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*
D011956:Receptors, Cell Surface; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins