Role of the hydrophobic domain in targeting caveolin-1 to lipid droplets.
Although caveolins normally reside in caveolae, they can accumulate on the surface of cytoplasmic lipid droplets (LDs). Here, we first provided support for our model that overaccumulation of caveolins in the endoplasmic reticulum (ER) diverts the proteins to nascent LDs budding from the ER. Next, we found that a mutant H-Ras, present on the cytoplasmic surface of the ER but lacking a hydrophobic peptide domain, did not accumulate on LDs. We used the fact that wild-type caveolin-1 accumulates in LDs after brefeldin A treatment or when linked to an ER retrieval motif to search for mutants defective in LD targeting. The hydrophobic domain, but no specific sequence therein, was required for LD targeting of caveolin-1. Certain Leu insertions blocked LD targeting, independently of hydrophobic domain length, but dependent on their position in the domain. We propose that proper packing of putative hydrophobic helices may be required for LD targeting of caveolin-1.
Ostermeyer
Anne G
AG
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5215, USA.
Ramcharan
Lynne T
LT
Zeng
Youchun
Y
Lublin
Douglas M
DM
Brown
Deborah A
DA
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D019556:COS Cells; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D011905:Genes, ras / Q000235:genetics; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000737:chemistry; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics
D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A