GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEINS ARE PREFERENTIALLY TARGETED TO THE BASOLATERAL SURFACE IN FISCHER RAT-THYROID EPITHELIAL-CELLS

Glycosylphosphatidylinositol (GPI) acts as an apical targeting signal in MDCK cells and other kidney and intestinal cell lines. In striking contrast with these model polarized cell lines, we show here that Fisc her rat thyroid (FRT) epithelial cells do not display a preferential a pical distribution of GPI-anchored proteins. Six out of nine detectabl e endogenous GPI-anchored proteins were localized on the basolateral s urface, whereas two others were apical and one was not polarized. Tran sfection of several model GPI proteins, previously shown to be apicall y targeted in MDCK cells, also led to unexpected results. While the ec todomain of decay accelerating factor (DAF) was apically secreted, 50% of the native, GPI-anchored form, of this protein was basolateral. Ad dition of a GPI anchor to the ectodomain of Herpes simplex gD-1, secre ted without polarity, led to basolateral localization of the fusion pr otein, gD1-DAF. Targeting experiments demonstrated that gD1-DAF was de livered vectorially from the Golgi apparatus to the basolateral surfac e. These results indicate that FRT cells have fundamental differences with MDCK cells with regard to the mechanisms for sorting GPI-anchored proteins: GPI is not an apical signal but, rather, it behaves as a ba solateral signal. The ''mutant'' behavior of FRT cells may provide clu es to the nature of the mechanisms that sort GPI-anchored proteins in epithelial cells.