| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Outline of Final Research Achievements |
In this study, I demonstrated the regulation mechanism of ATP11C flippase activity. ATP11C is a member of P4-ATPase family and flips phosphatidylserine (PS) from the exoplasmic to the cytosolic leaflet at the plasma membrane. ATP11C-a isoform was downregulated by the Ca2+-mediated PKC activation. The C-terminal cytoplasmic region of ATP11C-a was phosphorylated by PKC and subsequently allowed to form a di-leucine-like sorting motif, which serve as an endocytic signal. Endocytosis of ATP11C-a caused the decrease of phosphatidylserine flipping activity at the plasma membrane. Therefore, the PS flipping activity can be regulated by Ca-signal-mediated ATP11C-a endocytosis. Moreover, I discovered that a C-terminal splicing variant ATP11C-b localized to the restricted region of the plasma membrane while ATP11C-a to the entire plasma membrane. Moreover, the critical motif for the polarized localization of ATP11C-b was identified and a mechanism of the specific localization was elucidated.
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