Rey-Barroso, JavierAlvarez-Barrientos, AlbertoRico-Leo, EvaContador-Troca, MariaCarvajal-Gonzalez, Jose M.Echarri, Asierdel Pozo, Miguel AngelFernandez-Salguero, Pedro M.2018-10-252018-10-252014Cell Commun Signal. 2014; 12(1):571478-811Xhttp://hdl.handle.net/20.500.12105/6515Background: Adhesion and migration are relevant physiological functions that must be regulated by the cell under both normal and pathological conditions. The dioxin receptor (AhR) has emerged as a transcription factor regulating both processes in mesenchymal, epithelial and endothelial cells. Indirect results suggest that AhR could cooperate not only with additional transcription factors but also with membrane-associated proteins to drive such processes. Results: In this study, we have used immortalized and primary dermal fibroblasts from wild type (AhR+/+) and AhR-null (AhR-/-) mice to show that AhR modulates membrane distribution and mobilization of caveolin-1 (Cav-1) during directional cell migration. AhR co-immunoprecipitated with Cav-1 and a fraction of both proteins co-localized to detergent-resistant membrane microdomains (DRM). Consistent with a role of AhR in the process, AhR-/-cells had a significant reduction in Cav-1 in DRMs. Moreover, high cell density reduced AhR nuclear levels and moved Cav-1 from DRMs to the soluble membrane in AhR+/+ but not in AhR-/-cells. Tyrosine-14 phosphorylation had a complex role in the mechanism since its upregulation reduced Cav-1 in DRMs in both AhR+/+ and AhR-/-cells, despite the lower basal levels of Y-14-Cav-1 in the null cells. Fluorescence recovery after photobleaching revealed that AhR knock-down blocked Cav-1 transport to the plasma membrane, a deficit possibly influencing its depleted levels in DRMs. Membrane distribution of Cav-1 in AhR-null fibroblasts correlated with higher levels of cholesterol and with disrupted membrane microdomains, whereas addition of exogenous cholesterol changed the Cav-1 distribution of AhR+/+ cells to the null phenotype. Consistently, higher cholesterol levels enhanced caveolae-dependent endocytosis in AhR-null cells. Conclusions: These results suggest that AhR modulates Cav-1 distribution in migrating cells through the control of cholesterol-enriched membrane microdomains. Our study also supports the likely possibility of membrane-related, transcription factor independent, functions of AhR.engVoRhttp://creativecommons.org/licenses/by/4.0/Dioxin receptorCaveolin-1Membrane microdomainsEndocytosisCholesterolARYL-HYDROCARBON RECEPTORENDOTHELIAL-CELLSIN-VIVONUCLEAR TRANSLOCATIONDEPENDENT MECHANISMLIPID BODIESTGF-BETAEXPRESSIONPOLARIZATIONFIBROBLASTSAtribución 4.0 Internacional252389701210.1186/s12964-014-0057-7Cell Communication and Signalingopen access