Caveolae and clathrin-coated vesicles: Two possible internalization pathways for IFN-gamma and IFN-gamma receptor

Interferon-gamma (LFN-gamma) elicits a variety of activities following bind ing to its cell-surface-specific receptor (IFN-gammaR), This complex format ion leads to the activation of the Jak-STAT pathway. Several hypotheses hav e been proposed to explain the role and location of the receptor and its li gand in the signalling pathway. In vivo as well as in vitro, the present st udy shows that IFN-gamma and its receptor were internalized in different ce llular compartments including cytoplasmic matrix, mitochondria and nucleus. In order to analyse the internalization pathway of IFN-gamma and its recep tor, we have study in vivo and in vitro their colocalization with clathrin and caveolin by using double immunogold-labelling experiments using electro n microscopy. We demonstrate that TFN-gamma and IFN-gammaR were colocalized in the caveolin-containing structures and the clathrin-coated pits suggest ing that both internalization pathways may be used. This indicates that IFN -gamma and IFN-gammaR were internalized by these two different pathways, su ggesting two different intracellular routes probably for different target c ell-compartments. (C) 2001 Academic Press.