Bile acids target proteolipid nano-assemblies of EGFR and phosphatidic acid in the plasma membrane for stimulation of MAPK signaling

PloS One
Hong LiangYong Zhou

Abstract

Bile acids are critical biological detergents in the gastrointestinal tract and also act as messengers to regulate a multitude of intracellular signaling events, including mitogenic signaling, lipid metabolism and endo/exocytosis. In particular, bile acids stimulate many receptors and ion channels on the cell surface, the mechanisms of which are still poorly understood. Membrane-associating proteins depend on the local spatial distribution of lipids in the plasma membrane (PM) for their function. Here, we report that the highly amphipathic secondary bile acid deoxycholic acid (DCA), a major constituent in the human bile, at doses <1μM enhances the nanoclustering and the PM localization of phosphatidic acid (PA) but disrupts the local segregation of phosphatidylserine in the basolateral PM of the human colorectal adenocarcinoma Caco-2 cells. PA is a key structural component of the signaling nano-domains of epidermal growth factor receptor (EGFR) on the cell surface. We show that DCA promotes the co-localization between PA and EGFR, the PA-driven EGFR dimerization/oligomerization and EGFR signaling. Depletion of PA abolishes the stimulatory effects of DCA on the EGFR oligomerization and signaling. This effect occurs in the cultur...Continue Reading

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Citations

Jan 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kosuke MurakamiMary K Estes
Aug 14, 2020·Physiological Reviews·Alessia PerinoKristina Schoonjans

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Methods Mentioned

BETA
electron microscopy
biopsies

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