The RAB11A-Positive Compartment Is a Primary Platform for Autophagosome Assembly Mediated by WIPI2 Recognition of PI3P-RAB11A.
Gratian, Matthew J
Menzies, Fiona M
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Puri, C., Vicinanza, M., Ashkenazi, A., Gratian, M. J., Zhang, Q., Bento, C. F., Renna, M., et al. (2018). The RAB11A-Positive Compartment Is a Primary Platform for Autophagosome Assembly Mediated by WIPI2 Recognition of PI3P-RAB11A.. Developmental cell, 45 (1), 114-131.e8. https://doi.org/10.1016/j.devcel.2018.03.008
Autophagy is a critical pathway that degrades intra-cytoplasmic contents by engulfing them in double-membraned autophagosomes that are conjugated with LC3 family members. These membranes are specified by phosphatidylinositol 3- phosphate (PI3P), which recruits WIPI2, which, in turn, recruits ATG16L1 to specify the sites of LC3-conjugation. Conventionally, phosphatidylinositides act in concert with other proteins in targeting effectors to specific membranes. Here we describe that WIPI2 localizes to autophagic precursor membranes by binding RAB11A, a protein that specifies recycling endosomes and that PI3P is formed on RAB11A-positive membranes upon starvation. Loss of RAB11A impairs the recruitment and assembly of the autophagic machinery. RAB11A-positive membranes are a primary direct platform for canonical autophagosome formation that enables autophagy of the transferrin receptor and damaged mitochondria. While this compartment may receive membrane inputs from other sources to enable autophagosome biogenesis, RAB11A-positive membranes appear to be a compartment from which autophagosomes evolve.
Hela Cells, Endosomes, Humans, rab GTP-Binding Proteins, Phosphatidylinositol Phosphates, Carrier Proteins, Phosphate-Binding Proteins, Receptors, Transferrin, Microtubule-Associated Proteins, Membrane Proteins, Protein Transport, Autophagy, Autophagy-Related Proteins, Autophagosomes
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)
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External DOI: https://doi.org/10.1016/j.devcel.2018.03.008
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276427
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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