Entries in autophagy (1)


New paper out! LRSAM1, the E3 ligase crucial for anti-bacterial autophagy.

After what seems like forever our new paper came out in Cell Host and Microbe. It's open access, so go and download it!

In this paper we show that LRSAM1 is an E3 ubiquitin ligase that recognises intracellular bacteria and initiates the autophagy cascade. The majority of anti-Salmonella autophagy is dependant upon ubiquitination of bacteria, but the E3 ligase responsible was unknown (E3s select targets for ubiqutination and therefore generate the specificity of the ubiquitination process). LRSAM1 generates this specificity via a LRR (Leucine-Rich Repeat) domain which binds to intracellular bacteria, and a RING domain which drives ubiquitination. Once ubiquitin is attached to the bacteria, the autophagy machinery is recruited by ubiquitin-binding adaptor proteins.

Interestingly, LRSAM1 also directly binds one such ubiquitin-binding adaptor protein, suggesting that it might have a dual role, both generating and amplifying the autophagy-promoting signal by adaptor recruitment.

I am sure there is much more to discover about the role of LRSAM1, including what bacterial molecules trigger LRSAM1 recognition and binding and the targets of ubiquitination. These were questions we tried to address, but were unable to obtain satisfactory experimental data to definitively answer. I look forward to reading more about LRSAM1 in the future.