Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK activation. Role of cholesterol and actin cytoskeleton.
The endocytic compartment of eukaryotic cells is a complex intracellular structure involved in sorting, processing, and degradation of a great variety of internalized molecules. Recently, the uptake through caveolae has emerged as an alternative internalization pathway, which seems to be directly related with some signal transduction pathways. However, the mechanisms, molecules, and structures regulating the transport of caveolin from the cell surface into the endocytic compartment are largely unknown. In this study, normal quiescent fibroblasts (normal rat kidney (NRK)) were used to demonstrate that epidermal growth factor causes partial redistribution of caveolin from the cell surface into a cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin D or latrunculin A inhibits this pathway and the concomitant activation of Mek and mitotic-activated protein (MAP) kinase; however, if cells were pre-treated with filipin, cytochalasin D does not inhibit the phosphorylation of MAP kinase induced by epidermal growth factor. From these results we conclude that in NRK cells the intact actin cytoskeleton is necessary for the EGF-mediated transport of caveolin from the cell surface into the early endocytic compartment and the activation of MAP kinase pathway.
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Departament de Biologia Cel.lular, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) Facultat de Medicina, Universitat de Barcelona, Casanova 143, 08036-Barcelona, Spain.
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Pons
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Peiró
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Enrich
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D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005372:Filipin / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D051040:Vesicle-Associated Membrane Protein 3
D000199:Actins; D015415:Biomarkers; D019086:Bridged Bicyclo Compounds, Heterocyclic; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D013844:Thiazoles; D053778:Thiazolidines; D051040:Vesicle-Associated Membrane Protein 3; D015638:Cytochalasin D; D004815:Epidermal Growth Factor; D005372:Filipin; D002784:Cholesterol; D020928:Mitogen-Activated Protein Kinases; C037067:latrunculin A