Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - The small G protein may play a role in cholesterol efflux

Ken Ichi Hirano, Fumihiko Matsuura, Kosuke Tsukamoto, Zhongyan Zhang, Akifumi Matsuyama, Kenji Takaishi, Ryutaro Komuro, Tadashi Suehiro, Shizuya Yamashita, Yoshimi Takai, Yuji Matsuzawa

Research output: Contribution to journalArticle

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Abstract

Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport (RCT), a major protective system against atherosclerosis. However, most of the molecular mechanism for CE still remains to be clarified. In the present study, cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages (Mφ) from patients with Tangier disease (TD), a rare lipoprotein disorder with reduced CE. This small G protein is known to have many cell biological activities such as rearrangement of actin cytoskeleton and vesicular transport, however the association between this molecule and lipid transport has never been reported. We demonstrate that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, inversely ones expressing the dominant active form had increased CE. From these observations, we would like to raise a novel hypothesis that this type of small G protein may play a role in some steps of CE. To our knowledge, the present study is the first demonstration that the expression of this molecule is altered in cells from human disease. Copyright (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)275-279
Number of pages5
JournalFEBS Letters
Volume484
Issue number3
DOIs
Publication statusPublished - 10-11-2000

Fingerprint

Tangier Disease
rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Cholesterol
Madin Darby Canine Kidney Cells
Molecules
Macrophages
Fibroblasts
Bioactivity
Actin Cytoskeleton
Lipoproteins
Actins
Atherosclerosis
Demonstrations
Complementary DNA
Cells
Association reactions
Lipids

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hirano, Ken Ichi ; Matsuura, Fumihiko ; Tsukamoto, Kosuke ; Zhang, Zhongyan ; Matsuyama, Akifumi ; Takaishi, Kenji ; Komuro, Ryutaro ; Suehiro, Tadashi ; Yamashita, Shizuya ; Takai, Yoshimi ; Matsuzawa, Yuji. / Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - The small G protein may play a role in cholesterol efflux. In: FEBS Letters. 2000 ; Vol. 484, No. 3. pp. 275-279.
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abstract = "Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport (RCT), a major protective system against atherosclerosis. However, most of the molecular mechanism for CE still remains to be clarified. In the present study, cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages (Mφ) from patients with Tangier disease (TD), a rare lipoprotein disorder with reduced CE. This small G protein is known to have many cell biological activities such as rearrangement of actin cytoskeleton and vesicular transport, however the association between this molecule and lipid transport has never been reported. We demonstrate that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, inversely ones expressing the dominant active form had increased CE. From these observations, we would like to raise a novel hypothesis that this type of small G protein may play a role in some steps of CE. To our knowledge, the present study is the first demonstration that the expression of this molecule is altered in cells from human disease. Copyright (C) 2000 Federation of European Biochemical Societies.",
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Hirano, KI, Matsuura, F, Tsukamoto, K, Zhang, Z, Matsuyama, A, Takaishi, K, Komuro, R, Suehiro, T, Yamashita, S, Takai, Y & Matsuzawa, Y 2000, 'Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - The small G protein may play a role in cholesterol efflux', FEBS Letters, vol. 484, no. 3, pp. 275-279. https://doi.org/10.1016/S0014-5793(00)02171-2

Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - The small G protein may play a role in cholesterol efflux. / Hirano, Ken Ichi; Matsuura, Fumihiko; Tsukamoto, Kosuke; Zhang, Zhongyan; Matsuyama, Akifumi; Takaishi, Kenji; Komuro, Ryutaro; Suehiro, Tadashi; Yamashita, Shizuya; Takai, Yoshimi; Matsuzawa, Yuji.

In: FEBS Letters, Vol. 484, No. 3, 10.11.2000, p. 275-279.

Research output: Contribution to journalArticle

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T1 - Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - The small G protein may play a role in cholesterol efflux

AU - Hirano, Ken Ichi

AU - Matsuura, Fumihiko

AU - Tsukamoto, Kosuke

AU - Zhang, Zhongyan

AU - Matsuyama, Akifumi

AU - Takaishi, Kenji

AU - Komuro, Ryutaro

AU - Suehiro, Tadashi

AU - Yamashita, Shizuya

AU - Takai, Yoshimi

AU - Matsuzawa, Yuji

PY - 2000/11/10

Y1 - 2000/11/10

N2 - Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport (RCT), a major protective system against atherosclerosis. However, most of the molecular mechanism for CE still remains to be clarified. In the present study, cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages (Mφ) from patients with Tangier disease (TD), a rare lipoprotein disorder with reduced CE. This small G protein is known to have many cell biological activities such as rearrangement of actin cytoskeleton and vesicular transport, however the association between this molecule and lipid transport has never been reported. We demonstrate that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, inversely ones expressing the dominant active form had increased CE. From these observations, we would like to raise a novel hypothesis that this type of small G protein may play a role in some steps of CE. To our knowledge, the present study is the first demonstration that the expression of this molecule is altered in cells from human disease. Copyright (C) 2000 Federation of European Biochemical Societies.

AB - Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport (RCT), a major protective system against atherosclerosis. However, most of the molecular mechanism for CE still remains to be clarified. In the present study, cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages (Mφ) from patients with Tangier disease (TD), a rare lipoprotein disorder with reduced CE. This small G protein is known to have many cell biological activities such as rearrangement of actin cytoskeleton and vesicular transport, however the association between this molecule and lipid transport has never been reported. We demonstrate that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, inversely ones expressing the dominant active form had increased CE. From these observations, we would like to raise a novel hypothesis that this type of small G protein may play a role in some steps of CE. To our knowledge, the present study is the first demonstration that the expression of this molecule is altered in cells from human disease. Copyright (C) 2000 Federation of European Biochemical Societies.

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