Cholesterol-dependent regulation of intracellular localization of NPC1-L1

• Project/Area Number: 20590281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tottori University
• Principal Investigator: NINOMIYA Haruaki Tottori University, 医学部, 教授 (80212124)
• Co-Investigator(Renkei-kenkyūsha): HIGAKI Katumi 鳥取大学, 生命機能研究支援センター, 准教授 (90294321)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ニーマンピック / コレステロール / Rab / NPC1-L1 / トランスポート / ユビキチン

Research Abstract

By using transient gene expression system in HEK293 cells, we identified Rab proteins that participate in cholesterol-dependent intracellular sorting of Niemann-Pick C1-Like1 (NPC1-L1) protein. We also studied intracellular localization of endogenous NPC1-L1 in HepG2 cells and found that localization of the endogenous NPC1-L1 was also regulated in a cholesterol-dependent manner.

Research Products

• [Journal Article] Lysosomal accumulation of Trk protein in brain of GM1-gangliosidosis mouse and its restoration by chemical chaperone. (2011)
  • Author(s): Takamura A., Higaki K., Ninomiya H., Takai T., Matsuda J., Iida M., Ohno K., Suzuki Y., Nanba E.
  • Journal Title: J.Neurochem. in press
  • Peer Reviewed
• [Journal Article] Chemical chaperone therapy : chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency. (2011)
  • Author(s): Higaki K., Li L., Bahrudin U., Okuzawa S., Takamura A., Yamamoto K., Adachi K., Paraguison R.C., Takai T., Ikehata H., Tominaga L., Hisatome I., Iida M., Ogawa S., Matsuda J., Ninomiya H., Sakakibara Y., Ohno K., Suzuki Y., Nanba E.
  • Journal Title: Human Mut. in press
  • Peer Reviewed
• [Journal Article] Transcriptional activation of the anchoring protein SAP97 by heat shock factor (HSF)-1 stabilizes K(v) 1.5 channels in HL-1 cells. (2011)
  • Author(s): Ting Y., Morikawa K., Kurata Y., Li P., Bahrudin U., Mizuta E., Kato M., Miake J., Yamamoto Y., Yoshida A., Murata M., Inoue T., Nakai A., Shiota G, Higaki K., Nanba E., Ninomiya H., Shirayoshi Y., Hisatome I.
  • Journal Title: Br.J.Pharmacol. in press
  • Peer Reviewed
• [Journal Article] Copper incorporation into ceruloplasmin is regulated by Niemann-Pick C1 protein. (2011)
  • Author(s): Yanagimoto C., Harada M., Kumemura H., Abe M., Koga H., Sakata M., Kawaguchi T., Terada K., Hanada S., Taniguchi E., Ninomiya H., Ueno T., Sugiyama T., Sata M.
  • Journal Title: Hepatol Res. 41 Pages: 484-491
  • NAID: 10031144114
  • Peer Reviewed
• [Journal Article] Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability. (2011)
  • Author(s): Li P., Ninomiya H., Kurata Y., Kato M., Miake J., Yamamoto Y., Igawa O., Nakai A., Higaki K., Toyoda F., Wu J., Horie M., Matsuura H., Yoshida A., Shirayoshi Y., Hiraoka M., Hisatome I.
  • Journal Title: Cir.Res. 108 Pages: 458-468
  • NAID: 130002130408
  • Peer Reviewed
• [Journal Article] Chemical chaperone therapy : luciferase assay for screening of β-galactosidase mutations. (2010)
  • Author(s): Li L., Higaki K., Ninomiya H., Luan Z., Iida M., Ogawa S., Suzuki Y., Ohno K., Nanba E.
  • Journal Title: Mol.Genet.Metab. 101 Pages: 364-369
  • Peer Reviewed
• [Journal Article] A fluorescent sp^2-iminosugar with pharmacological chaperone activity for Gaucher disease : synthesis and intracellular distribution studies. (2010)
  • Author(s): Luan Z., Higaki K., Aguilar-Moncayo M., Li L., Ninomiya H., Nanba E., Ohno K., Garcia-Moreno M.I., Ortiz M.C., Garcia Fernandez J.M., Suzuki Y.
  • Journal Title: Chembiochem. 11 Pages: 2453-2464
  • Peer Reviewed
• [Journal Article] Different distribution of Cav3.2 and Cav3.1 transcripts encoding T-type Ca(2+) channels in the embryonic heart of mice. (2010)
  • Author(s): Mizuta E., Shirai M., Arakawa K., Hidaka K., Miake J., Ninomiya H., Kato M., Shigemasa C., Shirayoshi Y., Hisatome I., Morisaki T.
  • Journal Title: Biomed.Res. 31 Pages: 301-305
  • NAID: 130004903809
  • Peer Reviewed
• [Journal Article] The effect of N-octyl-β-valienamine on β-glucosidase activity in tissues of normal mice. (2010)
  • Author(s): Luan Z., Ninomiya H., Ohno K., Ogawa S., Kubo T., Iida M., Suzuki Y.
  • Journal Title: Brain Dev. 32 Pages: 805-809
  • NAID: 10029559648
  • Peer Reviewed
• [Journal Article] The pharmacological chaperone effect of N-octyl-β-valienamine on human mutant acid β-glucosidases. (2010)
  • Author(s): Luan Z., Li L., Ninomiya H., Ohno K., Ogawa S., Kubo T., Iida M., Suzuki Y.
  • Journal Title: Blood Cells Mol.Diseases 44 Pages: 48-54
  • Peer Reviewed
• [Journal Article] Effect of losartan and benzbromarone on the level of human urate transporter 1 mRNA. (2010)
  • Author(s): Nindita Y., Hamada T., Bahrudin U., Hosoyamada M., Ichida K., Iwai C., Urashima S., Kuwabara N., Utami S.B., Mizuta E., Yamada K., Igawa O., Shigemasa C., Ninomiya H., Tsuchihashi T., Hisatome I.
  • Journal Title: Arzneimittelforschung 60 Pages: 186-188
  • Peer Reviewed
• [Journal Article] Effects of a low-dose antihypertensive diuretic in combination with losartan, telmisartan, or candesartan on serum urate levels in hypertensive patients. (2010)
  • Author(s): Hamada T., Mizuta E., Kondo T., Hirai M., Yamada K., Kato M., Shigemasa C., Yamamoto Y., Ninomiya H., Igawa O., Hisatome I.
  • Journal Title: Arzneimittelforschung 60 Pages: 71-75
  • Peer Reviewed
• [Journal Article] Chemical chaperone therapy : luciferase assay for screening of β-galactosidase mutations (2010)
  • Author(s): Li, et al.
  • Journal Title: Mol.Genet.Metab. Volume: 101 Pages: 364-369
  • Peer Reviewed
• [Journal Article] The effect of N-octyl-β-valienamine on β-glucosidase activity in tissues of normal mice. (2010)
  • Author(s): Luan, et al.
  • Journal Title: Brain Dev. Volume: 32 Pages: 805-809
  • Peer Reviewed
• [Journal Article] The pharmacological chaperone effect of N-octyl-β-valienamine on human mutant acid β-glucosidases. (2010)
  • Author(s): Luan, et al.
  • Journal Title: Blood Cells Mol.Diseases Volume: 44 Pages: 48-54
  • Peer Reviewed
• [Journal Article] Chaperone activity of bicyclic nojirimycin analogues for Gaucher mutations in comparison with N-(n-nonyl)deoxynojirimycin. (2009)
  • Author(s): Luan Z., Higaki K., Aguilar-Moncayo M., Ninomiya H., Ohno K., Garcia-Moreno M.I., Ortiz M.C., Garcia Fernandez J.M., Suzuki Y.
  • Journal Title: Chembiochem. 23 Pages: 2780-2792
  • Peer Reviewed
• [Journal Article] Niemann-Pick C1 protein transports copper to the secretory compartment from late endosomes where ATP7B resides. (2009)
  • Author(s): Yanagimoto C., Harada M., Kumemura H., Koga H., Kawaguchi T., Terada K., Hanada S., Taniguchi E., Koizumi Y., Koyota S., Ninomiya H., Ueno T., Sugiyama T., Sata M.
  • Journal Title: Exp.Cell Res. 315 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Niemann-Pick C1 protein transports copper to the secretory compartment from late endosomes where ATP7B resides (2009)
  • Author(s): Yanagimoto, et al.
  • Journal Title: Exp.Cell Res. 315 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Stabilizing effects of eicosapentaenoic acid on Kvl.5 channel protein expressed in mammalian cells. (2009)
  • Author(s): Koshida, et al.
  • Journal Title: Eur.J.Pharmacol. 604 Pages: 93-102
  • Peer Reviewed
• [Journal Article] Chaperone activity of bicyclic nojirimycin analogues for Gaucher mutations in comparison with N-(n-nonyl)deoxynojirimycin. (2009)
  • Author(s): Luan, et al.
  • Journal Title: Chembiochem. 23 Pages: 2780-2792
  • Peer Reviewed
• [Journal Article] Brainstem neuropathology in a mouse model of Niemann-Pick disease type C. (2008)
  • Author(s): Luan, et al.
  • Journal Title: J. Neurol. Sci. 268 Pages: 108-116
  • Peer Reviewed
• [Journal Article] Enhanced autophagy and mitochondrial aberrations in murine GM1-gagliosidosis. (2008)
  • Author(s): Takamura, et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 367 Pages: 616-622
  • Peer Reviewed
• [Journal Article] Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy. (2008)
  • Author(s): Bahrudin, et al.
  • Journal Title: J Mol. Biol. 384 Pages: 896-907
  • Peer Reviewed
• [Remarks] ホームページ等
  • URL: http://www.ninomiya.med.tottori-u.ac.jp/homepage/
• [Remarks]
  • URL: http://www.ninomiya.med.tottori-u.ac.jp/homepage/
• [Remarks]
  • URL: http://www.ninomiya.med.tottori-u.ac.jp/homepage/
• [Remarks]
  • URL: http://www.asahi-net.or.jp/~ev6h-nnmy/