The ubiquitin-like modifier FAT10 decorates autophagy-targeted Salmonella and contributes to Salmonella resistance in mice

Spinnenhirn, Valentina; Farhan, Hesso; Basler, Michael; Aichem, Annette; Canaan, Allon; Gröttrup, Marcus

The ubiquitin-like modifier FAT10 decorates autophagy-targeted Salmonella and contributes to Salmonella resistance in mice

Dateien

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Datum

2014

Autor:innen

Spinnenhirn, Valentina

Canaan, Allon

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of cell science. 2014, 127(22), pp. 4883-4893. ISSN 0021-9533. eISSN 1477-9137. Available under: doi: 10.1242/jcs.152371

Zusammenfassung

Bacterial invasion of eukaryotic cells is counteracted by cell-autonomous innate immune mechanisms including xenophagy. The decoration of cytosolic bacteria by ubiquitylation and binding of galectin-8 leads to recruitment of autophagy adaptors like p62 (also known as SQSTM1), NDP52 (also known as CALCOCO2) and optineurin, which initiate the destruction of bacteria by xenophagy. Here, we show that the functionally barely characterized IFNγ- and TNFα-inducible ubiquitin-like modifier FAT10 (also known as ubiquitin D, UBD), which binds to the autophagy adaptor p62, but has not been shown to associate with pathogens before, is recruited to cytosolic Salmonella Typhimurium in human cells. FAT10-decorated S. Typhimurium were simultaneously decorated with ubiquitin, p62, NDP52 and the autophagy marker LC3B (MAP1LC3B). FAT10 colocalized with p62-positive microdomains on S. Typhimurium, whereas colocalization with NDP52 was only partial. A kinetic analysis revealed an early, but only transient, decoration of bacteria by FAT10, which resembled that of p62. Although bacterial replication was not detectably altered in FAT10-depleted or overexpressing cells in vitro, survival experiments revealed that NRAMP1-transgenic mice that were FAT10-deficient had a higher susceptibility to orally inoculated S. Typhimurium bacteria than NRAMP1-transgenic mice that were wild-type for FAT10. Taken together, our data suggest a role for FAT10 in the intracellular defense against bacteria.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Ubiquitin, FAT10, p62, Salmonella Typhimurium, Autophagy, Xenophagy

Zitieren

ISO 690

SPINNENHIRN, Valentina, Hesso FARHAN, Michael BASLER, Annette AICHEM, Allon CANAAN, Marcus GRÖTTRUP, 2014. The ubiquitin-like modifier FAT10 decorates autophagy-targeted Salmonella and contributes to Salmonella resistance in mice. In: Journal of cell science. 2014, 127(22), pp. 4883-4893. ISSN 0021-9533. eISSN 1477-9137. Available under: doi: 10.1242/jcs.152371

BibTex

@article{Spinnenhirn2014ubiqu-29805,
  year={2014},
  doi={10.1242/jcs.152371},
  title={The ubiquitin-like modifier FAT10 decorates autophagy-targeted Salmonella and contributes to Salmonella resistance in mice},
  number={22},
  volume={127},
  issn={0021-9533},
  journal={Journal of cell science},
  pages={4883--4893},
  author={Spinnenhirn, Valentina and Farhan, Hesso and Basler, Michael and Aichem, Annette and Canaan, Allon and Gröttrup, Marcus}
}

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Universitätsbibliographie

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