Caveolin-1 is required for fatty acid translocase (FAT/CD36) localization and function at the plasma membrane of mouse embryonic fibroblasts

Biochim Biophys Acta. 2006 Apr;1761(4):416-23. doi: 10.1016/j.bbalip.2006.03.016. Epub 2006 Apr 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism*
  • Caveolae / chemistry
  • Caveolae / metabolism*
  • Caveolae / ultrastructure
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Fatty Acids / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / physiology*
  • Mice
  • Mice, Knockout
  • Oleic Acids / chemistry
  • Oleic Acids / metabolism
  • Subcellular Fractions / metabolism
  • Succinimides / chemistry
  • Succinimides / metabolism

Substances

  • CD36 Antigens
  • Caveolin 1
  • Fatty Acids
  • Oleic Acids
  • Succinimides