ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2017

ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis

Résumé

The double-membrane-bound autophagosome is formed by the closure of a structure called the phagophore, origin of which is still unclear. The endoplasmic reticulum (ER) is clearly implicated in autophagosome biogenesis due to the presence of the omegasome subdomain positive for DFCP1, a phosphatidyl-inositol-3-phosphate (PI3P) binding protein. Contribution of other membrane sources, like the plasma membrane (PM), is still difficult to integrate in a global picture. Here we show that ER–plasma membrane contact sites are mobilized for autophagosome biogenesis, by direct implication of the tethering extended synaptotagmins (E-Syts) proteins. Imaging data revealed that early autophagic markers are recruited to E-Syt-containing domains during autophagy and that inhibition of E-Syts expression leads to a reduction in autophagosome biogenesis. Furthermore, we demonstrate that E-Syts are essential for autophagy-associated PI3P synthesis at the cortical ER membrane via the recruitment of VMP1, the stabilizing ER partner of the PI3KC3 complex. These results highlight the contribution of ER–plasma membrane tethers to autophagosome biogenesis regulation and support the importance of membrane contact sites in autophagy.
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée
Loading...

Dates et versions

inserm-01529671 , version 1 (31-05-2017)

Identifiants

Citer

Anna Chiara Nascimbeni, Francesca Giordano, Nicolas Dupont, Daniel Grasso, Maria I Vaccaro, et al.. ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis. EMBO Journal, 2017, 6 (14), pp.2018-2033. ⟨10.15252/embj.201797006⟩. ⟨inserm-01529671⟩
156 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More