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J Cell Sci. 2019 Jan 11;132(1). pii: jcs222612. doi: 10.1242/jcs.222612.

A SUMOylation-dependent switch of RAB7 governs intracellular life and pathogenesis of Salmonella Typhimurium.

Author information

1
Laboratory of Gut Inflammation and Infection Biology, Regional Centre for Biotechnology NCR Biotech Science Cluster 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad - 121 001 Haryana (NCR Delhi), India.
2
Manipal Acadamy of Higher Education, Manipal, Karnataka 576104, India.
3
Pediatric Biology Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad - Gurgaon Expressway, PO box #04, Faridabad - 121001 Haryana, India.
4
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Centre, Omaha, NE 68198, USA.
5
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Building 114, 16th Street, Charlestown, MA 02129, USA.
6
Laboratory of Gut Inflammation and Infection Biology, Regional Centre for Biotechnology NCR Biotech Science Cluster 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad - 121 001 Haryana (NCR Delhi), India cvsrikanth@rcb.res.in.

Abstract

Salmonella Typhimurium is an intracellular pathogen that causes gastroenteritis in humans. Aided by a battery of effector proteins, S. Typhimurium resides intracellularly in a specialized vesicle, called the Salmonella-containing vacuole (SCV) that utilizes the host endocytic vesicular transport pathway (VTP). Here, we probed the possible role of SUMOylation, a post-translation modification pathway, in SCV biology. Proteome analysis by complex mass-spectrometry (MS/MS) revealed a dramatically altered SUMO-proteome (SUMOylome) in S. Typhimurium-infected cells. RAB7, a component of VTP, was key among several crucial proteins identified in our study. Detailed MS/MS assays, in vitro SUMOylation assays and structural docking analysis revealed SUMOylation of RAB7 (RAB7A) specifically at lysine 175. A SUMOylation-deficient RAB7 mutant (RAB7K175R) displayed longer half-life, was beneficial to SCV dynamics and functionally deficient. Collectively, the data revealed that RAB7 SUMOylation blockade by S. Typhimurium ensures availability of long-lived but functionally compromised RAB7, which was beneficial to the pathogen. Overall, this SUMOylation-dependent switch of RAB7 controlled by S. Typhimurium is an unexpected mode of VTP pathway regulation, and unveils a mechanism of broad interest well beyond Salmonella-host crosstalk. This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

PTMs; RAB7; SUMOylation; Salmonella; Salmonella-containing vacuole; Vesicular transport system

PMID:
30510112
DOI:
10.1242/jcs.222612

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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