Journal
NATURE CELL BIOLOGY
Volume 18, Issue 6, Pages 657-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3360
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Funding
- INSERM
- CNRS
- University Paris Descartes
- ANR
- INCa
- Association pour la Recherche sur le Cancer (ARC)
- ERA-EDTA fellowship
- DFG [KU1504-5/1]
- Else-Kroner-Fresenius Stiftung [2011_A87]
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Autophagy is an adaptation mechanism that is vital for cellular homeostasis in response to various stress conditions. Previous reports indicate that there is a functional interaction between the primary cilium (PC) and autophagy. The PC, a microtubule-based structure present at the surface of numerous cell types, is a mechanical sensor. Here we show that autophagy induced by fluid flow regulates kidney epithelial cell volume in vitro and in vivo. PC ablation blocked autophagy induction and cell-volume regulation. In addition, inhibition of autophagy in ciliated cells impaired the flow-dependent regulation of cell volume. PC-dependent autophagy can be triggered either by mTOR inhibition or a mechanism dependent on the polycystin 2 channel. Only the LKB1-AMPK-mTOR signalling pathway was required for the flow-dependent regulation of cell volume by autophagy. These findings suggest that therapies regulating autophagy should be considered in developing treatments for PC-related diseases.
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