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PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress

Asma Boukhalfa, Anna Chiara Nascimbeni, Damien Ramel, Nicolas Dupont, Emilio Hirsch, Stephanie Gayral, Muriel Laffargue (), Patrice Codogno () and Etienne Morel ()
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Asma Boukhalfa: Université Paris Descartes-Sorbonne Paris Cité
Anna Chiara Nascimbeni: Université Paris Descartes-Sorbonne Paris Cité
Damien Ramel: Paul Sabatier University
Nicolas Dupont: Université Paris Descartes-Sorbonne Paris Cité
Emilio Hirsch: University of Torino
Stephanie Gayral: Paul Sabatier University
Muriel Laffargue: Paul Sabatier University
Patrice Codogno: Université Paris Descartes-Sorbonne Paris Cité
Etienne Morel: Université Paris Descartes-Sorbonne Paris Cité

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Cells subjected to stress situations mobilize specific membranes and proteins to initiate autophagy. Phosphatidylinositol-3-phosphate (PI3P), a crucial lipid in membrane dynamics, is known to be essential in this context. In addition to nutriments deprivation, autophagy is also triggered by fluid-flow induced shear stress in epithelial cells, and this specific autophagic response depends on primary cilium (PC) signaling and leads to cell size regulation. Here we report that PI3KC2α, required for ciliogenesis and PC functions, promotes the synthesis of a local pool of PI3P upon shear stress. We show that PI3KC2α depletion in cells subjected to shear stress abolishes ciliogenesis as well as the autophagy and related cell size regulation. We finally show that PI3KC2α and VPS34, the two main enzymes responsible for PI3P synthesis, have different roles during autophagy, depending on the type of cellular stress: while VPS34 is clearly required for starvation-induced autophagy, PI3KC2α participates only in shear stress-dependent autophagy.

Date: 2020
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DOI: 10.1038/s41467-019-14086-1

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