STRUCTURE-FUNCTION RELATIONSHIP OF CHOLESTEROL-ENRICHED MEMBRANE MICRODOMAINS

2010 Fiscal Year Final Research Report

• Project/Area Number: 20570116
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Tokyo Metropolitan Institute of Gerontology
• Principal Investigator: IWASHITA Yoshiko Tokyo Metropolitan Institute of Gerontology, 薬学部, 客員研究員 (50111498)
• Co-Investigator(Kenkyū-buntansha): IWASHITA Shintaro いわき明星大学, 薬学部, 教授 (90092147) ; INOMATA Mitsushi 地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 研究員 (30142649)
• Project Period (FY): 2008 – 2010
• Keywords: 生体膜 / Tリンパ球 / 膜機能ドメイン / コレステロール / シグナル伝達

Research Abstract

To study the structure-function relationship of membrane microdomains (lipid rafts) involved in signal transduction, we examined the alterations of lipid rafts in an age-associated decline in T-cell receptor signaling. By analyzing resting and stimulated mouse CD4^+ T cells, we found that the following alterations may be related to the age-dependent decline in T-cell receptor signaling : 1) age-dependent alterations in several lipid raft-associated molecules, and resulting dysregulation of a negative SFK (Src family kinase) regulatory system ; 2) age-associated up-regulation of PD-1-positive T cells that exhibit proliferative hyporesponsiveness; 3) altered localization/topology of cholesterol, one of major constituents of lipid rafts.

Research Products

• [Journal Article] Plasma membrane microdomains in aging disease. (2010)
  • Author(s): 岩下淑子, 嶋田有紀子, 林昌美, 猪股光司
  • Journal Title: Geriatr.Gerontol.Int. 10(suppl.1) Pages: S41-S52
  • Peer Reviewed
• [Journal Article] Use of dansyl-cholestanol as a probe of cholesterol behavior in membranes of living cells. (2010)
  • Author(s): Huang, H., McIntosh, A.L., Atshaves, B.P., Ohno-Iwashita Y., Kier, A.B., Schroeder, F.
  • Journal Title: J.Lipid Res. 51 Pages: 1157-1172
  • Peer Reviewed
• [Journal Article] 加齢に伴って増加するPD-1陽性Tリンパ球の正体は? (2010)
  • Author(s): 猪股光司、嶋田有紀子、林昌美、岩下淑子
  • Journal Title: 基礎老化研究 34 Pages: 23-27
• [Journal Article] Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells. (2009)
  • Author(s): Shimada Y., Hayashi M., Nagasaka, Y., Ohno-Iwashita Y, Inomata M
  • Journal Title: Exp.Gerontol. 44 Pages: 517-522
  • Peer Reviewed
• [Presentation] 加齢で増加するPD-1陽性CD4^+T細胞は刺激に対して不応答性である (2009)
  • Author(s): 嶋田有紀子、林昌美、長坂安彦、岩下淑子、猪股光司
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Presentation] 老齢マウスで見いだされた抑制型補助刺激シグナル受容体(PD-1)陽性CD4^+T細胞の性質 (2009)
  • Author(s): 猪股光司、嶋田有紀子、林昌美、岩下淑子
  • Organizer: 第32回日本基礎老化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 20090618-20090620
• [Presentation] Cholesterol gradient in biological membranes (2008)
  • Author(s): Murase-Tamada, K., Murate, M., Hayakawa, T., Nakamura, K., Ito, K., Shimada Y., Ohno-Iwashita Y., Kobayashi, T.
  • Organizer: International Symposium on Molecular System Life Sciences
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20081210-20081211
• [Presentation] 老齢マウスT細胞に於ける抑制型補助刺激シグナル受容体PD-1の発現充進とその意義 (2008)
  • Author(s): 猪股光司、嶋田有紀子、林昌美、岩下淑子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] 加齢に伴って増加するPD-1陽性CD4+T細胞の同定とその特徴 (2008)
  • Author(s): 嶋田有紀子、猪股光司、林昌美、岩下淑子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] Revisiting lipid asymmetry in red blood cells (2008)
  • Author(s): Murate, M., Shimada Y., Ohno-Iwashita Y., Umeda, M., Kobayashi, T.
  • Organizer: Flippases 2008
  • Place of Presentation: Ascona, Switzerl
  • Year and Date: 20081102-20081107
• [Presentation] 老齢マウスTリンパ球に於ける抑制型補助シグナル受容体の発現亢進 (2008)
  • Author(s): 猪股光司、林昌美、嶋田有紀子、岩下淑子
  • Organizer: 第31回日本基礎老化学会大会
  • Place of Presentation: 松本
  • Year and Date: 20080612-20080613
• [Book] Cholesterol-Binding Toxins Anti-cholesterol Antibodies as Structural Probes for Cholesterol Localization. Vol.51, p.597-621(Harris, J.R.ed.)(Cholesterol Binding Cholesterol Transport Proteins)(Chapter 22) Seies : Subcellular Biochemistry (2010)
  • Author(s): Ohno-Iwashita Y., Shimada, Y., Hayashi, M. Iwamoto, M., Iwashita, S., Inomata, M.
  • Publisher: Springer
• [Book] 生体膜の加齢変化、新老年学第3版 p.78-84(大内尉義,秋山弘子編集代表)東京 (2010)
  • Author(s): 岩下淑子
  • Publisher: 東京大学出版会
• [Book] Fluorescent sterols to study cholesterol trafficking in living cells. P.1-33(Miller, L.W.ed.)(Probes Tags to Study Biomolecular Function : for Proteins, RNA, Membranes) (2008)
  • Author(s): McIntosh, A.L., Huang, H., Atshaves, B.P., Storey, S.M., Gal legos, A.M., Spencer, T.A., Bittman, R., Ohno-Iwashita, Y., Kier, A.B., Schroeder, F.
  • Publisher: Wiley-VCH, Weinheim