| Title: |
Phosphoribosyl ubiquitination of SNARE proteins regulates autophagy during Legionella infection |
| Authors: |
Mukherjee,Rukmini; Bhattacharya,Anshu; Tomaskovic,Ines; Mello-Vieira,João; Brunstein,Melinda Elaine; Başoğlu,Marion; Veenendaal, Tineke; Bailey,Henry; Colby,Thomas; Misra,Mohit; Eimer,Stefan; Klumperman, Judith; Münch,Christian; Matic,Ivan; Dikic,Ivan; CMM Groep Klumperman; Cancer; CMM Sectie Celbiologie; Brain; Regenerative Medicine and Stem Cells |
| Publication Year: |
2025 |
| Subject Terms: |
Autophagy; Legionella pneumophila; Syntaxin17; Ubiquitin; Xenophagy; General Neuroscience; Molecular Biology; General Biochemistry,Genetics and Molecular Biology; General Immunology and Microbiology; Journal Article |
| Description: |
Legionella pneumophila is an intracellular pathogen that causes Legionnaires' disease. The bacteria release effector proteins, some of which remodel host autophagic-lysosomal pathways. One such effector is RavZ, which delipidates ATG8 proteins, making compromising autophagy in Legionella-infected cells. Here we show that SidE effectors also affect these pathways, by mediating phosphoribosyl-ubiquitination (PR-Ub) of the autophagic SNARE proteins STX17 and SNAP29. STX17 modification induces recruitment of STX17-positive membranes from the endoplasmic reticulum to Legionella-containing phagosomes, forming replicative vacuoles. Using proximity labeling, biochemistry and Legionella infection studies, we define a mechanism by which autophagy is hijacked by bacteria to recruit ER membranes to the bacterial vacuole, via a structure bearing autophagy markers but not fusing with lysosomes. Mass-spectrometric identification of PR-Ub sites and mutational studies show that phosphoribosyl-ubiquitination of STX17 alters its interaction with ATG14L, which causes ER membranes to be recruited to the bacterial vacuole in a PI3K-dependent manner. On the other hand, phosphoribosyl-ubiquitination of SNAP29 inhibits the formation of the autophagosomal SNARE complex (STX17-SNAP29-VAMP8) via steric hindrance, thus preventing the fusion of bacterial vacuoles with lysosomes. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0261-4189 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/466556 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/466556 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.1BD5585 |
| Database: |
BASE |