1991 Fiscal Year Final Research Report Summary
Pharmacological studies of calmodulin-dependent tau factor phosphorylation in cultured cerebellar granule cells.
| Project/Area Number |
02671056
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kumamoto Research (C) |
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Principal Investigator |
FUKUNAGA Kohji Kumamoto Univ. Med. Sch. Assistant Professor, 医学部, 講師 (90136721)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAKAWA Takashi Kumamoto Univ. Med. Sch. Research Associate, 医学部, 助手 (10230327)
MIYAMOTO Eishichi Kumamoto Univ. Medi. Sch. Professor, 医学部, 教授 (50109659)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Ca^<2+> / Calmodulin / Protein kinase / Cerebellar granule cells / Hippocampal neurons / NMDA receptor / Glutamate / Long-term potentiation |
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| Research Abstract |
Ca^<2+>/calmodulin-dependent protein kinase II(CaM kinase II), which is highly enriched in neural tissues, is a multifunctional protein kinase that is involved in regulation of biosynthesis and release of neurotransmitter, and expression of long-term potentiation(LTP)in CAl region of the hippocampus. Recently, it has been shown in vitro that autophosphorylation of Thr-286/287(alpha/beta subunits)in the CaM kinase II converts it from the Ca^<2+>-dependent form to a partially Ca^<2+>-independent species. We reported evidence for the formation of Ca^<2+>-independent CaM kinase II in cerebellar granule cells following the activation of the glutamate-induced NMDA receptor. In the granule cells, there was a good temporal correlation between autophosphorylation of Thr-287 in CaM kinase II and generation of Ca^<2+>-independent kinase activity. However, as brief exposure(30 sec)of granule cells to glutamate resulted in a relatively transient(<5 min)increase in the Ca^<2+>-independent activity o
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f CaM kinase II. Therefore, we have focused attention on the hippocampal tissue, since involvement of NMDA receptor in the LTP has been clearly shown in the tissue. In cultured hippocampal neurons, glutamate did elevated the Ca^<2+>-independent activity of CaM kinase II as in cerebellar granule cells. The maximal effect on the Ca^<2+>-independence was greater than that in the granule cells and the activity was more stable for at least 30 min in the continued presence of glutamate. In the experiments with _<32>P-labeled cells, the phosphorylation of MAP2 as well as autophosphorylation of CaM kinase II were found to be stimulated by the exposure to glutamate. These results were consistent with the hypothesis that the increase in the postsynaptic Ca^<2+> influx through the NMDA receptor-gated ion channel converts CaM kinase II to a constitutively active, Ca^<2+>-independent form in the hippocampal neurons, and results in an increase in the phosphorylation of target proteins such as MAP2 for the enzyme. Less
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