Role of ORP10 in NPC1L1-dependent cholesterol transport
| Project/Area Number |
15K08277
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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 |
General medical chemistry
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
Nakasone Naoe 鳥取大学, 医学部, 助教 (30632947)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Niemann-Pick C1 Like1 / ORP10 / cholesterol / コレステロール / 酸化ステロール結合蛋白質 |
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| Outline of Final Research Achievements |
In HEK cells stably expressing Niemann-Pick C1 Like 1 (NPC1L1)-YFP, overexpression of oxysterol-binding protein (OSBP)-related protein 10 (ORP10) increased the protein level of NPC1L1-YFP and enhanced cellular cholesterol uptake. The latter effect was more prominent with the ORP10 D254 isoform, which has been shown to predispose to hyper-LDL cholesterolemia, than with the N254 isoform. In reciprocal experiments, Co-immunoprecipitation (IP) assays showed that ORP10 interacted with both NPC1L1 and Numb via its N-terminal pleckstrin homology domain and C-terminal OSBP-related ligand-binding domain, respectively。Fluorescence resonance energy transfer (FRET) analyses revealed a clear difference in the intramolecular FRET efficacy between the two isoforms. These findings suggested that ORP10 regulates NPC1L1 internalization and that differential impact on NPC1L1-dependent cholesterol transport may underlie association of the D254 isoform with hyper-LDL cholesterolemia.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Inhibitory effects of local anesthetics on the proteasome and their biological actions2017
Author(s)
Bahrudin, U.; Unno, M.; Nishio, K.; Kita, A.; Li, P.; Kato, M.; Inoue, M.; Tsujitani, S.; Murakami, T.; Sugiyama, R.; Saeki, Y.; Obara, Y.; Tanaka, K.; Yamaguchi, H.; Sakane, I.; Kawata, Y.; Itoh, T.; Ninomiya, H.; Hisatome, I.; Morimoto, Y.
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 5079-5079
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells2017
Author(s)
Onohara, Takeshi; Hisatome, Ichiro; Kurata, Yasutaka; Li, Peili; Notsu, Tomomi; Morikawa, Kumi; Otani, Naoyuki; Yoshida, Akio; Iitsuka, Kazuhiko; Kato, Masaru; Miake, Junichiro; Ninomiya, Haruaki; Higaki, Katsumi; Shirayoshi, Yasuaki; Nishihara, Takashi; Itoh, Toshiyuki; Nakamura, Yoshinobu; Nishimura, Motonobu
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Journal Title
J. Arrhythmia,
Volume: 32
Issue: 3
Pages: 226-233
DOI
Related Report
Peer Reviewed / Open Access
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