title: Hydrophobic and basic domains target proteins to lipid droplets.
abstract: In recent years, progress in the study of the lateral organization of the plasma membrane has led to the proposal that mammalian cells use two different organelles to store lipids: intracellular lipid droplets (LDs) and plasma membrane caveolae. Experimental evidence suggests that caveolin (CAV) may act as a sensitive lipid-organizing molecule that physically connects these two lipid-storing organelles. Here, we determine the sequences necessary for efficient sorting of CAV to LDs. We show that targeting is a process cooperatively mediated by two motifs. CAV's central hydrophobic domain (Hyd) anchors CAV to the endoplasmic reticulum (ER). Next, positively charged sequences (Pos-Seqs) mediate sorting of CAVs into LDs. Our findings were confirmed by identifying an equivalent, non-conserved but functionally interchangeable Pos-Seq in ALDI, a bona fide LD-resident protein. Using this information, we were able to retarget a cytosolic protein and convert it to an LD-resident protein. Further studies suggest three requirements for targeting via this mechanism: the positive charge of the Pos-Seq, physical proximity between Pos-Seq and Hyd and a precise spatial orientation between both motifs. The study uncovers remarkable similarities with the signals that target proteins to the membrane of mitochondria and peroxisomes.
authors.affiliation: Departament de Biologia Cel.lular, Immunologia i Neurociències, Universitat de Barcelona, Casanova 143, 08036 Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ingelmo-Torres
authors.forename: Elena
authors.initials: E
authors.lastname: González-Moreno
authors.forename: Adam
authors.initials: A
authors.lastname: Kassan
authors.forename: Michael
authors.initials: M
authors.lastname: Hanzal-Bayer
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.forename: Albert
authors.initials: A
authors.lastname: Herms
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
authors.forename: John F
authors.initials: JF
authors.lastname: Hancock
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.forename: Marta
authors.initials: M
authors.lastname: Bosch
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Albert
authors.initials: A
authors.lastname: Pol
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*
chemical_list: D008055:Lipids; D011506:Proteins