title: Primary-cilium-dependent autophagy controls epithelial cell volume in response to fluid flow.
abstract: 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.
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Idil
authors.initials: I
authors.lastname: Orhon
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupont
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Zaidan
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Boitez
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Burtin
authors.affiliation: Institut Cochin, INSERM U1016-CNRS UMR 8104, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75014, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Capiod
authors.affiliation: Department of Nephrology, University Medical Center, Albert-Ludwig-University of Freiburg, D-79106 Freiburg, Germany.
authors.forename: Amandine
authors.initials: A
authors.lastname: Viau
authors.affiliation: INSERM UMR 1185, Université Paris-Sud 11, Kremlin-Bicêtre F-94276, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Beau
authors.affiliation: Department of Nephrology, University Medical Center, Albert-Ludwig-University of Freiburg, D-79106 Freiburg, Germany.|Center for Biological Signaling Studies (bioss), Albert-Ludwig-University, D-79104 Freiburg, Germany.
authors.forename: E Wolfgang
authors.initials: EW
authors.lastname: Kuehn
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Friedlander
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Terzi
authors.affiliation: Institut Necker Enfants-Malades (INEM), INSERM U1151-CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75993, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology; D000818:Animals; D001343:Autophagy; D002468:Cell Physiological Phenomena; D048429:Cell Size; D002923:Cilia / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D015151:Immunoblotting; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000502:physiology
chemical_list: C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases