STEROL CARRIER PROTEIN-2 IS INVOLVED IN CHOLESTEROL TRANSFER FROM THE ENDOPLASMIC-RETICULUM TO THE PLASMA-MEMBRANE IN HUMAN FIBROBLASTS

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 trans ported 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.