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Mol Biol Cell. 2017 Nov 1;28(22):3043-3056. doi: 10.1091/mbc.E17-01-0021. Epub 2017 Aug 30.

Shear stress induces noncanonical autophagy in intestinal epithelial monolayers.

Author information

1
Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232.
2
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
3
Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235.
4
Department of Food Science and Nutrition, Dong-A University, Busan 604-714, Republic of Korea.
5
Department of Biochemistry, Osaka International Cancer Institute, Osaka 541-8567, Japan.
6
Department of Biological Sciences, University of Toledo, Toledo, OH 43606.
7
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232.
8
Nashville VA Medical Center, Nashville, TN 37212.
9
Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232 ken.s.lau@vanderbilt.edu.

Abstract

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 contents 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 actin-rich microvilli that eventually generate the apical brush border, providing evidence that these structures possess mechanosensing ability. Importantly, we identified the molecular pathway that regulates large vacuole formation downstream from 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 noncanonical autophagy pathway in organized epithelial monolayers.

PMID:
28855375
PMCID:
PMC5662261
DOI:
10.1091/mbc.E17-01-0021
[Indexed for MEDLINE]
Free PMC Article

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