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

Matsuzawa, Yuji²  Hirano, Ken-ichi²  Tsukamoto, Kosuke²  Takai, Yoshimi¹  Suehiro, Tadashi³  Yamashita, Shizuya²  Matsuyama, Akifumi²  Matsuura, Fumihiko²  Takaishi, Kenji²  Komuro, Ryutaro²  Zhang, Zhongyan² 

[1]Department of Molecular Biology and Biochemistry, Graduate School of Medicine, B5, Osaka University 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan

[2]Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan

[3]Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan

关键词: Cdc42;    Cholesterol efflux;    Reverse cholesterol transport;    Small G protein;    Tangier disease;    Apo;    apolipoprotein;    CE;    cholesterol efflux;    DMEM;    Dulbecco's modified Eagle's medium;    HDL;    high density lipoprotein;    Mφ;    macrophages;    RCT;    reverse cholesterol transport;    RT-PCR;    reverse transcription-based polymerase chain reaction;    SR-BI;    scavenger receptor class B type I;    TD;    Tangier disease;   

DOI  :  10.1016/S0014-5793(00)02171-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown