Original Article

Caveolin-2 Is Targeted to Lipid Droplets, a New "Membrane Domain" in the Cell

Correspondence to: Toyoshi Fujimoto, Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya 466-8550, Japan. Tel:81 52-744-2000 Fax:81 52-744-2011 E-mail:tfujimot{at}med.nagoya-u.ac.jp.

Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the present study, we showed that caveolin-2, especially its ß isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation. Brefeldin A treatment induced further accumulation of caveolin-2 along with caveolin-1 in LD. Analysis of mouse caveolin-2 deletion mutants revealed that the central hydrophobic domain (residues 87–119) and the NH₂-terminal (residues 70–86) and COOH-terminal (residues 120–150) hydrophilic domains are all necessary for the localization in LD. The NH₂- and COOH-terminal domains appeared to be related to membrane binding and exit from ER, respectively, implying that caveolin-2 is synthesized and transported to LD as a membrane protein. In conjunction with recent findings that LD contain unesterified cholesterol and raft proteins, the result implies that the LD surface may function as a membrane domain. It also suggests that LD is related to trafficking of lipid molecules mediated by caveolins.

Key Words: lipid droplet, caveolin-2, caveolin-1, membrane domain, brefeldin A

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