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Wang, Yingxue, Ramos, Maria 
ORCID: https://orcid.org/0000-0002-6758-4069, Jefferson, Matthew, Zhang, Weijiao, Beraza, Naiara, Carding, Simon, Powell, Penny P. ORCID: https://orcid.org/0000-0002-5347-0490, Stewart, James P., Mayer, Ulrike ORCID: https://orcid.org/0000-0003-2328-0052 and Wileman, Thomas
(2022)
Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis.
Science Advances, 8 (43).
ISSN 2375-2548
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Abstract
The delivery of pathogens to lysosomes for degradation provides an important defense against infection. Degradation is enhanced when LC3 is conjugated to endosomes and phagosomes containing pathogens to facilitate fusion with lysosomes. In phagocytic cells, TLR signaling and Rubicon activate LC3-associated phagocytosis (LAP) where stabilization of the NADPH oxidase leads to sustained ROS production and raised vacuolar pH. Raised pH triggers the assembly of the vacuolar ATPase on the vacuole membrane where it binds ATG16L1 to recruit the core LC3 conjugation complex (ATG16L1:ATG5-12). This V-ATPase-ATG16L1 axis is also activated in nonphagocytic cells to conjugate LC3 to endosomes containing extracellular microbes. Pathogens provide additional signals for recruitment of LC3 when they raise vacuolar pH with pore-forming toxins and proteins, phospholipases, or specialized secretion systems. Many microbes secrete virulence factors to inhibit ROS production and/or the V-ATPase-ATG16L1 axis to slow LC3 recruitment and avoid degradation in lysosomes.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding: This work was supported by Biotechnology and Biological Sciences Research Council grant BB/R00904X/1 (T.W., P.P., U.M., S.C., and J.P.S.) and Biotechnology and Biological Sciences Research Council Institute Strategic Programme Gut Microbes and Health BB/R012490/1, BBS/E/F/000PR10353, and BBS/E/F/000PR10355 (T.W., S.C., and N.B.) and the UKRI Biotechnology and Biological Sciences Research Council Norwich Research Park Biosciences Doctoral Training Partnership BB/T008717/1 (M.R.). |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 15 Dec 2022 04:11 |
| Last Modified: | 19 Oct 2023 03:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/90170 |
| DOI: | 10.1126/sciadv.abn3298 |
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