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Cell Host Microbe DOI:10.1016/j.chom.2012.10.019

The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium.

Publication TypeJournal Article
Year of Publication2012
AuthorsHuett, A, Heath, RJ, Begun, J, Sassi, SO, Baxt, LA, Vyas, JM, Goldberg, MB, Xavier, RJ
JournalCell Host Microbe
Volume12
Issue6
Pages778-90
Date Published2012 Dec 13
ISSN1934-6069
KeywordsAutophagy, Gene Knockout Techniques, HeLa Cells, Humans, Protein Structure, Tertiary, Salmonella typhimurium, Ubiquitin, Ubiquitin-Protein Ligases
Abstract

Several species of pathogenic bacteria replicate within an intracellular vacuolar niche. Bacteria that escape into the cytosol are captured by the autophagic pathway and targeted for lysosomal degradation, representing a defense against bacterial exploitation of the host cytosol. Autophagic capture of Salmonella Typhimurium occurs predominantly via generation of a polyubiquitin signal around cytosolic bacteria, binding of adaptor proteins, and recruitment of autophagic machinery. However, the components mediating bacterial target selection and ubiquitination remain obscure. We identify LRSAM1 as the E3 ligase responsible for anti-Salmonella autophagy-associated ubiquitination. LRSAM1 localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal; these functions require LRSAM1's leucine-rich repeat and RING domains, respectively. Using cells from LRSAM1-deficient individuals, we confirm that LRSAM1 is required for ubiquitination associated with intracellular bacteria but dispensable for ubiquitination of aggregated proteins. LRSAM1 is therefore a bacterial recognition protein and ubiquitin ligase that defends the cytoplasm from invasive pathogens.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1931-3128(12)00391-5
DOI10.1016/j.chom.2012.10.019
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23245322?dopt=Abstract

Alternate JournalCell Host Microbe
PubMed ID23245322
PubMed Central IDPMC3785244
Grant ListR01 DK060049 / DK / NIDDK NIH HHS / United States
R01 DK069344 / DK / NIDDK NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R21 AI103676 / AI / NIAID NIH HHS / United States
R01 DK092405 / DK / NIDDK NIH HHS / United States
U01 DK062432 / DK / NIDDK NIH HHS / United States
R01 AI081724 / AI / NIAID NIH HHS / United States
R56 AI081724 / AI / NIAID NIH HHS / United States
U01 R01 DK060049 / DK / NIDDK NIH HHS / United States
R01 DK083756 / DK / NIDDK NIH HHS / United States
R01 AI092084 / AI / NIAID NIH HHS / United States
R01 DK097485 / DK / NIDDK NIH HHS / United States