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Shear stress induces non-canonical autophagic flux in intestinal epithelial monolayers.


Kim SW , Ehrman J , Ahn MR , Kondo J , Lopez AAM , Oh YS , Kim HX , Crawley SW , Goldenring JR , Tyska MJ , Rericha EC , Lau KS , . Molecular biology of the cell. 2017 8 30; ().


Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen.  We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular content, within polarizing intestinal epithelial cell monolayers.  These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume.   We find that shear forces are sensed by these cells through actin-rich microvilli that eventually generate the apical brush border, providing one of the first evidence that these structures possess mechanosensing ability. Importantly, we identified the molecular pathway that regulates large vacuole formation downstream of mechanostimulation to involve central components of the autophagy pathway, including ATG5 and LC3, but not Beclin. Together, our results establish a novel link between the actin-rich microvilli, the macroscopic transport of fluids across cells, and the non-canonical autophagy pathway in organized epithelial monolayers.