Hydrophobic and basic domains target proteins to lipid droplets.

Hydrophobic and basic domains target proteins to lipid droplets.
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DOI:
10.1111/j.1600-0854.2009.00994.x
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发表时间:
2009-12
期刊:
Traffic (Copenhagen, Denmark)
影响因子:
--
通讯作者:
Pol A
Pol A
中科院分区:
其他
文献类型:
--
作者:
Ingelmo-Torres M;González-Moreno E;Kassan A;Hanzal-Bayer M;Tebar F;Herms A;Grewal T;Hancock JF;Enrich C;Bosch M;Gross SP;Parton RG;Pol A

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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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