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Caveolae and clathrin-coated vesicles: two possible internalization pathways for IFN-gamma and IFN-gamma receptor
R Sadir1, A Lambert, H Lortat-Jacob
1CNRS UMR 5578, Université Claude Bernard-Lyon 1, Villeurbanne, France.
Abstract:
Interferon-gamma (IFN-gamma) elicits a variety of activities following binding to its cell-surface-specific receptor (IFN-gammaR). This complex formation leads to the activation of the Jak-STAT pathway. Several hypotheses have been proposed to explain the role and location of the receptor and its ligand in the signalling pathway. In vivo as well as in vitro, the present study shows that IFN-gamma and its receptor were internalized in different cellular compartments including cytoplasmic matrix, mitochondria and nucleus. In order to analyse the internalization pathway of IFN-gamma and its receptor, we have study in vivo and in vitro their colocalization with clathrin and caveolin by using double immunogold-labelling experiments using electron microscopy. We demonstrate that IFN-gamma and IFN-gammaR were colocalized in the caveolin-containing structures and the clathrin-coated pits suggesting that both internalization pathways may be used. This indicates that IFN-gamma and IFN-gammaR were internalized by these two different pathways, suggesting two different intracellular routes probably for different target cell-compartments.
Insights
Interferon-gamma (IFN-gamma) and its receptor (IFN-gammaR) are internalized into cells via both clathrin and caveolin pathways. This suggests distinct intracellular routes for IFN-gamma signaling to different cellular compartments.
Area of Science:
- Cellular Biology
- Immunology
- Molecular Signaling
Background:
- Interferon-gamma (IFN-gamma) binding to its receptor (IFN-gammaR) activates the Jak-STAT pathway.
- The precise mechanisms and cellular locations of IFN-gamma and IFN-gammaR internalization remain incompletely understood.
Purpose of the Study:
- To investigate the internalization pathways of IFN-gamma and IFN-gammaR.
- To determine the colocalization of IFN-gamma and IFN-gammaR with known endocytic markers.
Main Methods:
- In vivo and in vitro studies.
- Double immunogold-labeling using electron microscopy.
- Colocalization analysis with clathrin and caveolin.
Main Results:
- IFN-gamma and IFN-gammaR were found in various cellular compartments, including the cytoplasm, mitochondria, and nucleus.
- Colocalization with clathrin-coated pits and caveolin-containing structures was observed.
- Evidence suggests dual internalization pathways for IFN-gamma and IFN-gammaR.
Conclusions:
- IFN-gamma and IFN-gammaR utilize both clathrin-dependent and caveolin-dependent endocytic pathways.
- These distinct internalization routes may direct the ligand-receptor complex to different intracellular targets.
- This dual pathway mechanism could facilitate diverse cellular responses mediated by IFN-gamma.