FUNCTIONAL SIGNIFICANCE OF LIPID DROPLETS AS A NEW MEMBRANE DOMAIN

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Lipid droplets(LDs) have been regarded simply as a depot of lipids in specially differentiated cells, e.g., white adipose cells. But in fact LDs are found virtually in any cell type, but their function has been left ambiguous. In the present study, we attempted to examine the physiological function of LDs mainly in non-adipose cells, and obtained the following results.1)Caveolins, especially caveolin-2β, was preferentially localized in the surface of LDs. The central hydrophobic portion of caveolin-2βwas necessary for the localization. Other caveolins, including caveolin-1 and caveolin-2α were also localized to LDs when the ER-to-Golgi transport was inhibited by brefeldin A.2)The LD surface was shown to be a phospholipid monolayer containing free cholesterol. The fatty acid composition of the LD phospholipids was unique and different from that of the ER and rafts.3)ADRP (or adipophilin), a protein specifically localized to LDs in non-adipose cells, was targeted to LDs by using different sequence cues from caveolins. Two redundant signals were found in the N and C termini of the ADRP molecule.4)ADRP was shown to bind to ARF1,and was dissociated from LDs when cells were treated with brefeldin A or GDP-bound ARF1.5)By proteomic analysis of purified LDs, Rab18 was identified as an LD-specific protein.Overexpression of Rab18 eliminated ADRP from the LD surface, and induced formation of the LD-ER apposition. The same apposition was formed when the expression of ADRP was knocked down by RNA interference or when cells were treated by brefeldin A.These results indicate that LDs do not simply store excessive lipids, but may be involved in various important functions including intracellular lipid trafficking and metabolism.