title: Sterol carrier protein-2 is involved in cholesterol transfer from the endoplasmic reticulum to the plasma membrane in human fibroblasts.
abstract: The cellular mechanism of cholesterol transport from the endoplasmic reticulum to the plasma membrane is currently unknown. To assess the possibility that sterol carrier protein-2 (SCP-2) is involved in this transport, we studied the time course of newly synthesized cholesterol incorporation in the plasma membrane of normal and SCP-2-deficient (Zellweger syndrome) human fibroblasts. Cholesterol transfer was rapid, cytoskeleton-independent, and Golgi-independent in normal cells, but it was slower, cytoskeleton-dependent, and Golgi-dependent in SCP-2-deficient cells. After SCP-2 antisense oligonucleotides treatment of normal fibroblasts, the rapid transport was reduced by 81% with a simultaneous increase of the slower one. These results suggest that in normal fibroblasts the major fraction of newly synthesized cholesterol is transported to the plasma membrane by a SCP-2-dependent mechanism. In contrast, in SCP-2-deficient cells, newly synthesized cholesterol leaves the endoplasmic reticulum by a cytoskeleton/Golgi-dependent mechanism.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Puglielli
authors.forename: A
authors.initials: A
authors.lastname: Rigotti
authors.forename: A V
authors.initials: AV
authors.lastname: Greco
authors.forename: M J
authors.initials: MJ
authors.lastname: Santos
authors.forename: F
authors.initials: F
authors.lastname: Nervi
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010940:Plant Proteins
chemical_list: D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D010940:Plant Proteins; C072087:sterol carrier proteins; D002784:Cholesterol; D003078:Colchicine