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

ANNA CHIARA NASCIMBENI, FRANCESCA GIORDANO, NICOLAS DUPONT, DANIEL GRASSO, MARIA I VACCARO, PATRICE CODOGNO & ETIENNE MOREL

EMBO JOURNAL

NATURE PUBLISHING GROUP

Año: 2017 vol. 36 p. 2018 - 2033

0261-4189

EMBO J. 2017 May 26. pii: e201797006. doi: 10.15252/embj.201797006. [Epub ahead of print]ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis.Nascimbeni AC1,2, Giordano F3,4, Dupont N1,2, Grasso D5, Vaccaro MI5, Codogno P1,2, Morel E6,2.Author informationAbstractThe 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.© 2017 The Authors.