Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Outline of Final Research Achievements |
Phosphatidylinositol 3-kinases (PI3Ks) are the family of lipid kinases responsible for the generation of 3’-phosphoinositides. We have recently reported that class II a-isoform PI3K (C2a) plays a crucial role in developmental and pathological angiogenesis, and is indispensable for the maintenance of the VE-cadherin-mediated EC barrier function and receptor endocytosis. These defects result in impaired vascular homeostasis under the pathophysiological conditions. In this study, we found that among myotubularin-related protein (MTMR) family members, the expression of MTMRx is relatively abundant in ECs. We found that, in HUVECs, MTMRx was localized mainly in the endosomes. Next we analyzed the phenotype of MTMRx global KO mice. MTMRx mice showed normally development but die perinatally. We conclude that C2a regulates vascular homeostasis through controlling PI(3)P+-membrane trafficking, cooperating with MTMRx in ECs.
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