2019 Fiscal Year Final Research Report
Regulatory mechanism of phospholipids flippase ATP11C in non-apoptotic cells
| Project/Area Number |
17K08270
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | フリッパーゼ / ホスファチジルセリン / ATP11C / 極性細胞 / P4-ATPase |
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| Outline of Final Research Achievements |
ATP11C, a member of the P4-ATPase family, translocates phosphatidylserine (PS) and phosphatidylethanolamine at the plasma membrane. Although there are two N-terminal and three C-terminal splicing variants in human ATP11C and only latter variants in mouse ATP11C, the functional differences between isoforms have been neglected. We previously showed that the C-terminus of ATP11C-a (C1-form) is critical for its endocytosis upon PKC activation. However, C2- and C3-forms of ATP11C were not endocytosed upon PKC activation. Importantly, we found that ATP11C-b (C2-form) localized to the limited region of the plasma membrane in polarized cells, such as migrating Pro B cells and invasive breast cancer cells although ATP11C-a (C1-form) localized to the plasma membrane uniformly in either polarized or non-polarized cells. These results suggest that ATP11C-b isoform regulates the PS distribution at the distinct place of the plasma membrane in polarized cells.
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| Free Research Field |
分子細胞生物
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| Academic Significance and Societal Importance of the Research Achievements |
ホスファチジルセリン(PS)の露出制御は、アポトーシス細胞など死にゆく細胞では詳しく解明されてきたが、正常な細胞での可逆的かつ一過的なものに関してはよくわかっていなかった。その中で今般、ATP11Cが重要な役割を担うことが明らかとなり、その2種類のアイソフォームで明確に局在と制御機構が異なることが明らかとなった。このことは、一つの細胞の中でも、ATP11Cの２つのアイソフォームが作用することで局所によりPSの露出制御が異なっていることを示すものである。これまで明らかにされていなかった一過的なPS露出の生理作用を解明していく上で重要な発見であると考えられる。
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