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We show here that overexpression of the recycling\/exocytic Rab GTPase Rab8 rescued the late endosomal cholesterol deposition and sphingolipid mistrafficking in NPC fibroblasts. Rab8 redistributed cholesterol from late endosomes to the cell periphery and stimulated cholesterol efflux to the ABCA1-ligand apolipoprotein A-I (apoA-I) without increasing cholesterol esterification. Depletion of Rab8 from wild-type fibroblasts resulted in cholesterol deposition within late endosomal compartments. This cholesterol accumulation was accompanied by impaired clearance of LDL-cholesterol from endocytic circuits to apoA-I and could not be bypassed by liver X receptor activation. Our findings establish Rab8 as a key component of the regulatory machinery that leads to ABCA1-dependent removal of cholesterol from endocytic circuits.<\/jats:p>","DOI":"10.1091\/mbc.e06-07-0575","type":"journal-article","created":{"date-parts":[[2006,10,19]],"date-time":"2006-10-19T00:48:17Z","timestamp":1161218897000},"page":"47-56","source":"Crossref","is-referenced-by-count":88,"title":["Rab8-dependent Recycling Promotes Endosomal Cholesterol Removal in Normal and Sphingolipidosis Cells"],"prefix":"10.1091","volume":"18","author":[{"given":"Matts D.","family":"Linder","sequence":"first","affiliation":[{"name":"*Institute of Biomedicine\/Anatomy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riikka-Liisa","family":"Uronen","sequence":"additional","affiliation":[{"name":"*Institute of Biomedicine\/Anatomy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarit","family":"H\u00f6ltt\u00e4-Vuori","sequence":"additional","affiliation":[{"name":"*Institute of Biomedicine\/Anatomy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Sluijs","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Per\u00e4nen","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Ikonen","sequence":"additional","affiliation":[{"name":"*Institute of Biomedicine\/Anatomy and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1161\/01.ATV.0000014804.35824.DA","volume":"22","author":"Aiello R. 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