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J Cell Biol. 2018 Dec 3;217(12):4199-4214. doi: 10.1083/jcb.201802155. Epub 2018 Oct 11.

Salmonella SipA mimics a cognate SNARE for host Syntaxin8 to promote fusion with early endosomes.

Author information

1
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
2
Indian Institute of Science Education and Research, Pune, India.
3
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India amitabha@nii.res.in.

Abstract

SipA is a major effector of Salmonella, which causes gastroenteritis and enteric fever. Caspase-3 cleaves SipA into two domains: the C-terminal domain regulates actin polymerization, whereas the function of the N terminus is unknown. We show that the cleaved SipA N terminus binds and recruits host Syntaxin8 (Syn8) to Salmonella-containing vacuoles (SCVs). The SipA N terminus contains a SNARE motif with a conserved arginine residue like mammalian R-SNAREs. SipAR204Q and SipA1-435R204Q do not bind Syn8, demonstrating that SipA mimics a cognate R-SNARE for Syn8. Consequently, Salmonella lacking SipA or that express the SipA1-435R204Q SNARE mutant are unable to recruit Syn8 to SCVs. Finally, we show that SipA mimicking an R-SNARE recruits Syn8, Syn13, and Syn7 to the SCV and promotes its fusion with early endosomes to potentially arrest its maturation. Our results reveal that SipA functionally substitutes endogenous SNAREs in order to hijack the host trafficking pathway and promote Salmonella survival.

PMID:
30309979
PMCID:
PMC6279372
DOI:
10.1083/jcb.201802155
[Indexed for MEDLINE]
Free PMC Article

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