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bioRxiv · 10.1101/2021.05.19.444771

A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis

Li, S.·Yan, R.·Xu, J.·Zhao, S.·Ma, X.·Sun, Q.·Zhang, M.·Li, Y.·Liu, J.-J. G.·Chen, L.·Xu, K.·Ge, L.
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Abstract

Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system remodels has been poorly understood. Here we identify a new type of membrane contact formed between the ER-Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER-Golgi system, which is essential for promoting autophagosome biogenesis induced by different stress stimuli. The ERGIC-ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2-5 nm) between the two compartments. The tight membrane contact allows the ERES-located SEC12 to transactivate COPII assembly on the ERGIC. In addition, a portion of SEC12 also relocates to the ERGIC. Through both mechanisms, the ERGIC-ERES contact promotes formation of the ERGIC-derived COPII vesicle, a membrane precursor of the autophagosome. The ERGIC-ERES contact is physically and functionally different from the TFG-mediated ERGIC-ERES adjunction involved in secretory protein transport, and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.

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Li, S., Yan, R., Xu, J., Zhao, S., Ma, X., Sun, Q., Zhang, M., Li, Y., Liu, J.-J. G., Chen, L., Xu, K., Ge, L.. 2021-05-19. A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis. https://doi.org/10.1101/2021.05.19.444771

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