Hydrophobic and Basic Domains Target Proteins to Lipid Droplets

被引:65
作者
Ingelmo-Torres, Mercedes [1 ,2 ]
Gonzalez-Moreno, Elena [2 ]
Kassan, Adam [1 ]
Hanzal-Bayer, Michael [3 ]
Tebar, Francesc [2 ]
Herms, Albert [1 ]
Grewal, Thomas [4 ]
Hancock, John F. [3 ]
Enrich, Carlos [1 ,2 ]
Bosch, Marta [1 ]
Gross, Steven P. [5 ]
Parton, Robert G. [3 ,6 ]
Pol, Albert [1 ]
机构
[1] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain
[2] Univ Barcelona, Fac Med, Dept Biol Cellular Immunol & Neurociencies, E-08036 Barcelona, Spain
[3] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia
[4] Univ Sydney, Fac Pharm, Dept Pharmaceut Chem, Sydney, NSW 2006, Australia
[5] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA
[6] Univ Queensland, Ctr Microscopy & Microanal, Brisbane, Qld 4072, Australia
基金
英国医学研究理事会;
关键词
ALDI; caveolin; endoplasmic reticulum; lipid droplets; sorting signal; HEPATITIS-C VIRUS; DIFFERENTIATION-RELATED PROTEIN; MITOCHONDRIAL OUTER-MEMBRANE; DOMINANT-NEGATIVE MUTANT; ENDOPLASMIC-RETICULUM; CORE PROTEIN; STORAGE DROPLETS; SACCHAROMYCES-CEREVISIAE; GOLGI-COMPLEX; OIL BODIES;
D O I
10.1111/j.1600-0854.2009.00994.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1785 / 1801
页数:17
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