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

• Published in: FEBS letters Vol. 484; no. 3; pp. 275 - 279
• Main Authors: Hirano, Ken-ichi, Matsuura, Fumihiko, Tsukamoto, Kosuke, Zhang, Zhongyan, Matsuyama, Akifumi, Takaishi, Kenji, Komuro, Ryutaro, Suehiro, Tadashi, Yamashita, Shizuya, Takai, Yoshimi, Matsuzawa, Yuji
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 10.11.2000
• Subjects: Animals; Apo, apolipoprotein; Cdc42; cdc42 GTP-Binding Protein - genetics; cdc42 GTP-Binding Protein - metabolism; CE, cholesterol efflux; Cell Line; Cells, Cultured; Cholesterol efflux; DMEM, Dulbecco's modified Eagle's medium; Dogs; Fibroblasts - enzymology; Gene Library; HDL, high density lipoprotein; Humans; Macrophages - enzymology; Male; Middle Aged; Mφ, macrophages; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; RCT, reverse cholesterol transport; Reverse cholesterol transport; RT-PCR, reverse transcription-based polymerase chain reaction; Skin - enzymology; Small G protein; SR-BI, scavenger receptor class B type I; Tangier disease; Tangier Disease - enzymology; Tangier Disease - genetics; TD, Tangier disease; Transfection; Mφ, macrophages; TD, Tangier disease; CE, cholesterol efflux; Reverse cholesterol transport; HDL, high density lipoprotein; SR-BI, scavenger receptor class B type I; RCT, reverse cholesterol transport; RT-PCR, reverse transcription-based polymerase chain reaction; DMEM, Dulbecco’s modified Eagle’s medium; Tangier disease; Small G protein; Apo, apolipoprotein; Cdc42; Cholesterol efflux
• DOI: 10.1016/S0014-5793(00)02171-2
• ISSN: 0014-5793

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.