Lisanti M P, Tang Z L, Sargiacomo M
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
J Cell Biol. 1993 Nov;123(3):595-604. doi: 10.1083/jcb.123.3.595.
Glycosyl-phosphatidylinositol (GPI)-linked proteins are transported to the apical surface of epithelial cells where they undergo cholesterol-dependent clustering in membrane micro-invaginations, termed caveolae or plasmalemmal vesicles. However, the sorting machinery responsible for this caveolar-clustering mechanism remains unknown. Using transfected MDCK cells as a model system, we have identified a complex of cell surface molecules (80, 50, 40, 22-24, and 14 kD) that interact in a pH- and cholesterol-dependent fashion with an apical recombinant GPI-linked protein. A major component of this hetero-oligomeric protein complex is caveolin, a type II transmembrane protein. As this hetero-oligomeric caveolin complex is detectable almost immediately after caveolin synthesis, our results suggest that caveolae may assemble intracellularly during transport to the cell surface. As such, our studies have implications for understanding both the intracellular biogenesis of caveolae and their subsequent interactions with GPI-linked proteins in epithelia and other cell types.
糖基磷脂酰肌醇（GPI）连接蛋白被转运到上皮细胞的顶端表面，在那里它们在膜微凹陷（称为小窝或质膜小泡）中经历胆固醇依赖性聚集。然而，负责这种小窝聚集机制的分选机制仍然未知。我们使用转染的MDCK细胞作为模型系统，鉴定了一组细胞表面分子（80、50、40、22 - 24和14 kD），它们以pH和胆固醇依赖性方式与顶端重组GPI连接蛋白相互作用。这种异源寡聚蛋白复合物的主要成分是小窝蛋白，一种II型跨膜蛋白。由于这种异源寡聚小窝蛋白复合物在小窝蛋白合成后几乎立即就能检测到，我们的结果表明小窝可能在转运到细胞表面的过程中在细胞内组装。因此，我们的研究对于理解小窝的细胞内生物发生以及它们随后在上皮细胞和其他细胞类型中与GPI连接蛋白的相互作用具有重要意义。
