共 59 条
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
来源:
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.
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页码:1785 / 1801
页数:17
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