title: Accumulation of RhoA, RhoB, RhoG, and Rac1 in fibroblasts from Tangier disease subjects suggests a regulatory role of Rho family proteins in cholesterol efflux.
abstract: Tangier disease (TD) is an inherited disorder of lipid metabolism characterized by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl ester accumulation and reduced cholesterol excretion in response to HDL apolipoproteins. Molecular defects in the ATP binding cassette transporter 1 (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role in the translocation of cholesterol across the plasma membrane, and defective ABCA1 causes cholesterol storage in TD cells. However, the exact relationship of many of the biochemical and morphological abnormalities in TD to ABCA1 is unknown. Since small GTP-binding proteins are important regulators of many cellular functions, we characterized these proteins in normal and TD fibroblasts using the [alpha-32P]GTP overlay technique and Western blotting of SDS and isoelectric focusing gels. Our results indicate that GTP-binding proteins of the Rho family (RhoA, RhoB, RhoG, Rac-1) are enriched in fibroblasts from TD patients. The accumulation of small G proteins may have potential implications for the TD phenotype and the regulation of cholesterol excretion in TD cells.
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Munster, Albert-Schweitzer-Str. 33, 48149 Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Utech
authors.forename: G
authors.initials: G
authors.lastname: Höbbel
authors.forename: S
authors.initials: S
authors.lastname: Rust
authors.forename: H
authors.initials: H
authors.lastname: Reinecke
authors.forename: G
authors.initials: G
authors.lastname: Assmann
authors.forename: M
authors.initials: M
authors.lastname: Walter
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000302:isolation & purification / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D012016:Reference Values; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013631:Tangier Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C075397:RHOG protein, human; D006160:Guanosine Triphosphate; D002784:Cholesterol; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein