How does ORP11 ameliorate cholesterol accumulation in NPC cells?
| Project/Area Number |
18K15066
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 49010:Pathological biochemistry-related
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | ニーマンピック / コレステロール / ORP蛋白質 / ニーマン・ピック / 小胞輸送 / Niemann-Pick C1 / 酸化ステロール結合蛋白質 |
|---|
| Outline of Final Research Achievements |
A CHO cell line that lacks Niemann-Pick C1 is characterized by an accumulation of cholesterol in the late endosome/lysosome (LE/Lys). Human oxysterol-binding protein (OSBP)-related protein (ORP) family consists of 12 members, OSBP and ORP1-11. We found that overexpression of ORP11 could ameliorate cholesterol accumulation in CHO/NPC1(-) cells. The ORP11 effect was abolished by a dominant-negative form of Rab9. Co-immunoprecipitation of expressed proteins and in vitro binding assay of recombinant proteins demonstrated a physical interaction between Rab9 and ORP11. ORP11 also interacted with ORP9 and evidence was presented for the presence of a ternary complex that consisted of Rab9, ORP11 and ORP9. Finally, the ORP11 effect was abolished by a dominant-negative form of ORP9. These findings suggested the presence of an NPC1-independent, LE-to-Golgi lipid transport machinery that involved Rab9, ORP11 and ORP9.
|
| Academic Significance and Societal Importance of the Research Achievements |
ニーマン・ピック病Ｃ型(NPC)の原因遺伝子産物 NPC1の欠損細胞では、エンドゾームにコレステロールが蓄積する。本研究では、NPC1欠損細胞にORP11を過剰発現するとコレステロールの蓄積が減少・消失すること、この効果には低分子量G蛋白質Rab9が必要であることを発見した。これらの結果は、ORP11がRab9の新規エフェクターでありNPC治療のターゲットとなる可能性を示唆しており、学術的価値は高い。
|
Report
(4 results)
Research Products
(3 results)
