Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum
Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum
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DOI：
10.1074/jbc.m111240200
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发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Nabi, IR
中科院分区：
文献类型：
--
作者：
Le, PU;Guay, G;Nabi, IR
小窝是质膜上的烧瓶状内陷，其构成富含胆固醇和鞘脂的抗洗涤剂膜结构域的亚类，并表达小窝蛋白（一种小窝外壳蛋白）。自分泌运动因子受体（AMF-R）稳定地定位于小窝，并且胆固醇提取试剂甲基-β-环糊精抑制其内化至内质网，从而在这种独特的受体介导的内吞途径中暗示小窝。奇怪的是，AMF-R对甲基-β-环糊精敏感的内质网内吞作用的速率在ras和ab 1转化的NIH-3 T3细胞中增加，所述细胞表达显著降低水平的小窝蛋白和很少的小窝。通过腺病毒表达系统过表达发动蛋白K44 A显性失活突变体诱导转化细胞中对甲基-g-环糊精提取敏感的小窝内陷，而不增加小窝蛋白表达。发动蛋白K44 A表达进一步抑制AMF-R介导的内质网内吞作用。在未转化和转化的NIH-3 T3细胞中。腺病毒表达的小窝蛋白-1还诱导转化的NIH-3 T3细胞中的小窝，并将AMF-R介导的内质网内吞作用降低至未转化的NIH-3 T3细胞中观察到的水平。因此，富含胆固醇的抗洗涤剂膜结构域或糖脂筏独立于小窝蛋白-1表达而内陷，以通过快速动力蛋白依赖性的从质膜脱离形成内吞能力的小窝囊泡。小窝蛋白-1稳定小窝的质膜结合，从而作为小窝介导的AMF-R对内质网的内吞作用的负调节剂。
Caveolae are flask-shaped invaginations at the plasma membrane that constitute a subclass of detergent-resistant membrane domains enriched in cholesterol and sphingolipids and that express caveolin, a caveolar coat protein. Autocrine motility factor receptor (AMF-R) is stably localized to caveolae, and the cholesterol extracting reagent, methyl-beta-cyclodextrin, inhibits its internalization to the endoplasmic reticulum implicating caveolae in this distinct receptor-mediated endocytic pathway. Curiously, the rate of methyl-beta-cyclodextrin-sensitive endocytosis of AMF-R to the endoplasmic reticulum is increased in ras- and abl-transformed NIH-3T3 cells that express significantly reduced levels of caveolin and few caveolae. Overexpression of the dynamin K44A dominant negative mutant via an adenovirus expression system induces caveolar invaginations sensitive to methyl-g-cyclodextrin extraction in the transformed cells without increasing caveolin expression. Dynamin K44A expression further inhibits AMF-R-mediated endocytosis to the endoplasmic reticulum. in untransformed and transformed NIH-3T3 cells. Adenoviral expression of caveolin-1 also induces caveolae in the transformed NIH-3T3 cells and reduces AMF-R-mediated endocytosis to the endoplasmic reticulum to levels observed in untransformed NIH-3T3 cells. Cholesterol-rich detergent-resistant membrane domains or glycolipid rafts therefore invaginate independently of caveolin-1 expression to form endocytosis-competent caveolar vesicles via rapid dynamin-dependent detachment from the plasma membrane. Caveolin-1 stabilizes the plasma membrane association of caveolae and thereby acts as a negative regulator of the caveolae-mediated endocytosis of AMF-R to the endoplasmic reticulum.