Li Yifu, Prinz William A
Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2004 Oct 22;279(43):45226-34. doi: 10.1074/jbc.M407600200. Epub 2004 Aug 16.
Little is known about the mechanisms of intracellular sterol transport or how cells maintain the high sterol concentration of the plasma membrane (PM). Here we demonstrate that two inducible ATP-binding cassette (ABC) transporters (Aus1p and Pdr11p) mediate nonvesicular movement of PM sterol to the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. This transport facilitates exogenous sterol uptake, which we find requires steryl ester synthesis in the ER. Surprisingly, while expression of Aus1p and Pdr11p significantly increases sterol movement from PM to ER, it does not alter intracellular sterol distribution. Thus, ER sterol is likely rapidly returned to the PM when it is not esterified in the ER. We show that the propensity of PM sterols to be moved to the ER is largely determined by their affinity for sterol sphingolipid-enriched microdomains (rafts). Our findings suggest that raft association is a primary determinant of sterol accumulation in the PM and that Aus1p and Pdr11p facilitate sterol uptake by increasing the cycling of sterol between the PM and ER.
关于细胞内固醇转运机制或细胞如何维持质膜（PM）的高固醇浓度，我们所知甚少。在此，我们证明了酿酒酵母中有两种诱导型ATP结合盒（ABC）转运蛋白（Aus1p和Pdr11p）介导质膜固醇向内质网（ER）的非囊泡转运。这种转运促进了外源性固醇的摄取，我们发现这需要在内质网中合成固醇酯。令人惊讶的是，虽然Aus1p和Pdr11p的表达显著增加了固醇从质膜向内质网的转运，但它并没有改变细胞内固醇的分布。因此，当内质网中的固醇未被酯化时，内质网固醇可能会迅速返回质膜。我们表明，质膜固醇转移至内质网的倾向很大程度上取决于它们对富含固醇鞘脂的微结构域（脂筏）的亲和力。我们的研究结果表明，脂筏结合是质膜中固醇积累的主要决定因素，并且Aus1p和Pdr11p通过增加固醇在质膜和内质网之间的循环来促进固醇摄取。
