PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress.
Animals
Autophagy
/ physiology
Cell Line
Cell Size
Cilia
/ physiology
Class III Phosphatidylinositol 3-Kinases
/ genetics
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Humans
Kidney Tubules, Proximal
/ cytology
Mice, Inbred C57BL
Mice, Mutant Strains
Phosphatidylinositol 3-Kinases
/ genetics
Phosphatidylinositol Phosphates
/ metabolism
Stress, Mechanical
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
31
03
2019
accepted:
09
12
2019
entrez:
17
1
2020
pubmed:
17
1
2020
medline:
14
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31941925
doi: 10.1038/s41467-019-14086-1
pii: 10.1038/s41467-019-14086-1
pmc: PMC6962367
doi:
Substances chimiques
Phosphatidylinositol Phosphates
0
phosphatidylinositol 3-phosphate
0
Class III Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3C2A protein, human
EC 2.7.1.137
PIK3C3 protein, mouse
EC 2.7.1.137
Pik3c2a protein, mouse
EC 2.7.1.137
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
294Commentaires et corrections
Type : CommentIn
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