| Project/Area Number |
18H02594
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉村 信一郎 大阪大学, 医学系研究科, 講師 (60584521)
森脇 健太 東邦大学, 医学部, 准教授 (70778068)
國井 政孝 大阪大学, 医学系研究科, 助教 (80614768)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 細胞極性 / 極性輸送 / 上皮細胞 / Rab / SNARE |
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| Outline of Final Research Achievements |
We identified many vacuoles distinct from lysosomes in enucleating erythroblasts. Different sets of proteins were identified between EHBP1L1 KO and WT RBC membranes by massspec. We identified candidate binding proteins for EHBP1L1.VAMP8, syntaxin1B were found to be binding proteins for SNAP23 and their knockdown perturbed the transport of N-cadherin to the plasma membrane of neural progenitor cells. By live imaging, we showed that VAMP8 and N-cadherin were co-migrated in cell processes. We identified novel Rab11 binding protein, RELCH. RELCH binds OSBP and Rab11-RELCH-OSBP complex localized between the recycling endosomes and the trans Golgi network (TGN) and plays a role in cholesterol transport from the recycling endosomes to the TGN.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで知られていなかった赤芽球の脱核における膜輸送の分子機構を明らかにしつつある。これは異なる細胞で普遍的な極性輸送に分子機構があることを示唆する。また効率的に赤血球を作製できれば貧血の治療に役立つ可能性がある。SNAP23のKOマウスで大脳小脳の低形成が生じたため、SNAP23が脳の疾患の原因遺伝子に関係する可能性が示された。またcadherinの細胞膜への輸送経路の解明に寄与出来た。未知の点が多いコレステロール輸送にRab11やその結合分子RELCH, OSBPが関与する結果を得ることが出来た。コレステロールの輸送異常は様々な疾患を生じるため、その治療等に寄与する可能性もある。
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