The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium

Huett, Alan, Heath, Robert J., Begun, Jakob, Sassi, Slim O., Baxt, Leigh A., Vyas, Jatin M., Goldberg, Marcia B. and Xavier, Ramnik J. (2012) The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium. Cell Host and Microbe, 12 6: 778-790. doi:10.1016/j.chom.2012.10.019


Author Huett, Alan
Heath, Robert J.
Begun, Jakob
Sassi, Slim O.
Baxt, Leigh A.
Vyas, Jatin M.
Goldberg, Marcia B.
Xavier, Ramnik J.
Title The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium
Formatted title
The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular salmonella typhimurium
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1931-3128
1934-6069
Publication date 2012-12-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.chom.2012.10.019
Open Access Status DOI
Volume 12
Issue 6
Start page 778
End page 790
Total pages 13
Place of publication Cambridge, United States
Publisher Cell Press
Language eng
Subject 2400 Immunology and Microbiology
1306 Cancer Research
1312 Molecular Biology
Formatted 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.
Keyword Microbiology
Parasitology
Virology
Microbiology
Parasitology
Virology
MICROBIOLOGY
PARASITOLOGY
VIROLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 DK083756
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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Created: Wed, 24 Sep 2014, 20:06:57 EST by Ms Kate Rowe on behalf of Mater Research Institute-UQ