TY - JOUR
T1 - CaM kinase II in long-term potentiation
AU - Fukunaga, Kohji
AU - Muller, Dominique
AU - Miyamoto, Eishichi
N1 - Funding Information:
This work was supported in part by grant-in-aid for scientific research and for scientific research on priority areas from the Ministry of Education, Science and Culture (E.M. and K.F.) and by the Swiss National Research Foundation (D.M.).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996/4
Y1 - 1996/4
N2 - The observation that autophosphorylation converts CaM kinase II from the Ca2+-dependent form to the Ca2+-independent form has led to speculation that the formation of the Ca2+-independent form of the enzyme could encode frequency of synaptic usage and serve as a molecular explanation of 'memory'. In cultured rat hippocampal neurons, glutamate elevated the Ca2+-independent activity of CaM kinase II through autophosphorylation, and this response was blocked by an NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5). In addition, we confirmed that high, but not low frequency stimulation, applied to two groups of CA1 afferents in the rat hippocampus, resulted in LTP induction with concomitant long-lasting increases in Ca2+-independent and total activities of CaM kinase II. In experiments with 32P-labeled hippocampal slices, the LTP induction in the CA1 region was associated with increases in autophosphorylation of both α and β subunits of CaM kinase II 1 h after LTP induction. Significant increases in phosphorylation of endogenous CaM kinase II substrates, synapsin I and microtubule-associated protein 2 (MAP2), which are originally located in presynaptic and postsynaptic regions, respectively, were also observed in the same slice. All these changes were prevented when high frequency stimulation was applied in the presence of AP5 or a calmodulin antagonist, calmidazolium. Furthermore, in vitro phosphorylation of the AMPA receptor by CaM kinase II was reported in the postsynaptic density and infusion of the constitutively active CaM kinase II into the hippocampal neurons enhanced kainate-induced response. These results support the idea that CaM kinase II contributes to the induction of hippocampal LTP in both postsynaptic and presynaptic regions through phosphorylation of target proteins such as the AMPA receptor, MAP2 and synapsin I.
AB - The observation that autophosphorylation converts CaM kinase II from the Ca2+-dependent form to the Ca2+-independent form has led to speculation that the formation of the Ca2+-independent form of the enzyme could encode frequency of synaptic usage and serve as a molecular explanation of 'memory'. In cultured rat hippocampal neurons, glutamate elevated the Ca2+-independent activity of CaM kinase II through autophosphorylation, and this response was blocked by an NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5). In addition, we confirmed that high, but not low frequency stimulation, applied to two groups of CA1 afferents in the rat hippocampus, resulted in LTP induction with concomitant long-lasting increases in Ca2+-independent and total activities of CaM kinase II. In experiments with 32P-labeled hippocampal slices, the LTP induction in the CA1 region was associated with increases in autophosphorylation of both α and β subunits of CaM kinase II 1 h after LTP induction. Significant increases in phosphorylation of endogenous CaM kinase II substrates, synapsin I and microtubule-associated protein 2 (MAP2), which are originally located in presynaptic and postsynaptic regions, respectively, were also observed in the same slice. All these changes were prevented when high frequency stimulation was applied in the presence of AP5 or a calmodulin antagonist, calmidazolium. Furthermore, in vitro phosphorylation of the AMPA receptor by CaM kinase II was reported in the postsynaptic density and infusion of the constitutively active CaM kinase II into the hippocampal neurons enhanced kainate-induced response. These results support the idea that CaM kinase II contributes to the induction of hippocampal LTP in both postsynaptic and presynaptic regions through phosphorylation of target proteins such as the AMPA receptor, MAP2 and synapsin I.
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U2 - 10.1016/0197-0186(95)00097-6
DO - 10.1016/0197-0186(95)00097-6
M3 - Review article
C2 - 8740440
AN - SCOPUS:0029988641
VL - 28
SP - 343
EP - 358
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 4
ER -