title: Caveolin-1 is required for fatty acid translocase (FAT/CD36) localization and function at the plasma membrane of mouse embryonic fibroblasts.
abstract: Several lines of evidence suggest that lipid rafts are involved in cellular fatty acid uptake and influence fatty acid translocase (FAT/CD36) function. However, it remains unknown whether caveolae, a specialized raft type, are required for this mechanism. Here, we show that wild-type (WT) mouse embryonic fibroblasts (MEFs) and caveolin-1 knockout (KO) MEFs, which are devoid of caveolae, have comparable overall expression of FAT/CD36 protein but altered subcellular FAT/CD36 localization and function. In WT MEFs, FAT/CD36 was isolated with both lipid raft enriched detergent-resistant membranes (DRMs) and detergent-soluble membranes (DSMs), whereas in cav-1 KO cells it was exclusively associated with DSMs. Subcellular fractionation demonstrated that FAT/CD36 in WT MEFs was localized intracellularly and at the plasma membrane level while in cav-1 KO MEFs it was absent from the plasma membrane. This mistargeting of FAT/CD36 in cav-1 KO cells resulted in reduced fatty acid uptake compared to WT controls. Adenoviral expression of caveolin-1 in KO MEFs induced caveolae formation, redirection of FAT/CD36 to the plasma membrane and rescue of fatty acid uptake. In conclusion, our data provide evidence that caveolin-1 is necessary to target FAT/CD36 to the plasma membrane. Caveolin-1 may influence fatty acid uptake by regulating surface availability of FAT/CD36.
authors.affiliation: Department of Internal Medicine IV, Ruprechts-Karls-University Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Ring
authors.forename: Soazig
authors.initials: S
authors.lastname: Le Lay
authors.forename: Juergen
authors.initials: J
authors.lastname: Pohl
authors.forename: Paul
authors.initials: P
authors.lastname: Verkade
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009829:Oleic Acids / Q000737:chemistry / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013388:Succinimides / Q000737:chemistry / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D051242:Caveolin 1; D005227:Fatty Acids; D009829:Oleic Acids; D013388:Succinimides