[Calcium signaling and brain functions].
Calcium signaling plays a critical role in various cell types by activation of receptors and Ca2+ channels in response to neurotransmitters, hormones, growth, factors etc. Although a variety of functions of intracellular Ca2+ are reported, Ca2+/calmodulin-dependent protein kinases (CaMK) are involved in their mediation. We have been studying on CaMK I, II, III, IV and K in the dynamic regulation in the cells in relation to functions. In this study, we elucidated the structures of the isoforms of CaMKII subunits with nuclear translocation signal (NTS). NTS is included in the variable domain following the regulatory domain with a sequence of KKRK. The isoforms of CaMK subunits such as alpha B, gamma A, gamma A.B, delta 3 and delta 7 contain NTS in the sequences of the structures. Transfection of the isoforms with NTS into NG108-15 cells stimulated the expression of brain-derived neurotrophic factor in the cytoplasm. Activation of CaMKII and IV and mitogen-activated protein kinase (MAPK) was observed during long-term potentiation (LTP) induction in the CA1 area of hippocampus. The activation of CaMKII was sustained for a long period, whereas that of CaMKIV and MAPK was transient. The results suggest that CaMKII is involved in LTP induction, while CaMKIV and MAPK are rather involved in LTP maintenance. We present and discuss our recent studies on regulation of CaMKs in neuronal functions.
Miyamoto
E
E
Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan.
Fukunaga
K
K
Takeuchi
Y
Y
Yamamoto
H
H
Kasahara
J
J
Liu
Jie
J
D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation; D009473:Neuronal Plasticity
D019208:Brain-Derived Neurotrophic Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium