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

被引:108
作者
PUGLIELLI, L
RIGOTTI, A
GRECO, AV
SANTOS, MJ
NERVI, F
机构
[1] PONTIFICIA UNIV CATOLICA CHILE, FAC MED, DEPT GASTROENTEROL, SANTIAGO, CHILE
[2] PONTIFICIA UNIV CATOLICA CHILE, FAC MED, CTR PARA PREVENT & TRATAMIENTO CANC DIGEST, SANTIAGO, CHILE
[3] PONTIFICIA UNIV CATOLICA CHILE, FAC CIENCIAS BIOL, DEPT BIOL CELULAR & MOLEC, SANTIAGO, CHILE
[4] UNIV CATTOLICA SACRO CUORE, FAC MED & CHIRURG, IST MED INTERNA, I-00198 ROME, ITALY
关键词
D O I
10.1074/jbc.270.32.18723
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:18723 / 18726
页数:4
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