| Co-Investigator(Kenkyū-buntansha) |
MAEHAMA Tomohiko TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, INVESTIGATOR, 東京都臨床医学総合研究所, 研究員 (40322755)
YOKOZEKI Takeaki UNIVERSITY OF TSUKUBA, GRADUATE SCHOOL OF COMPREHENSIVE HUMAN SCIENCES, ASSOCIATE PROFESSOR, 大学院・人間総合科学研究科, 講師 (80373405)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2005: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Research Abstract |
We have investigated activation mechanisms and physiological functions of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) which produces the pleiotropic phospholipid, phosphatidylinositol 4,5-bisphosphate, in neuronal cells. So far, we have obtained the results shown below.
1.Regulation of dendritic spine by PIP5Kβ.
In mouse, PIP5Kβ was found that its expression pattern was almost the same as that of the spine marker protein PSD95 during development, and it was fractionated in the same fraction of PSD95,suggesting that PIP5Kβ functions in spines. Furthermore, we found that overexpression of wild type of PIP5Kβ in primary culture of mouse hippocampal neurons decreased the number of spines. In contrast, overexpression of a kinase-deficient mutant of PIP5Kβ increased spines. These results suggest that PIP5Kβ negatively regulates spine formation.
2. Novel interaction of PIP5Kγ661 with AP-2 adaptor complex plays a crucial role in synaptic vesicle endocytosis in hippocampal neurons.
We found that PIP5Kγ661, of three PIP5K isozymes, α, β, and γ, and two splicing variants of PIP5Kγ, γ635 and γ661, specifically interacts with AP-2 complex. PIP5Kγ661 bound to the Ear domain of AP-2 through its C-terminal 26 amino acid tail. Furthermore, it was found that the interaction between PIP5Kγ661 and AP-2 is essential for depolarizing-dependent synaptic vesicle endocytosis.
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