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ER –plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI 3P synthesis
Author(s) -
Nascimbeni Anna Chiara,
Giordano Francesca,
Dupont Nicolas,
Grasso Daniel,
Vaccaro Maria I,
Codogno Patrice,
Morel Etienne
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797006
Subject(s) - library science , art , political science , humanities , art history , computer science
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 DFCP 1, a phosphatidyl‐inositol‐3‐phosphate ( PI 3P) 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 PI 3P synthesis at the cortical ER membrane via the recruitment of VMP 1, the stabilizing ER partner of the PI 3 KC 3 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.