!!!NEW!!! A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress #autophagy #ER_phagy #ER_Literature #ufmylation biorxiv.org/content/10.110… a thread 1/8 
Using native mass spec, ITC, SPR and cell biology, we showed that it binds ATG8 via a non-canonical AIM, that we named Shuffled AIM (sAIM)- IDWG 3/8
C53 undergoes autophagic flux specifically during ER stress, shown with several stress factors, cell bio and biochemistry assays 4/8
Since it is a cytosolic protein, we thought it could have access to ER lumen via these 4 scenarios (1) UPR sensors (2) ERAD machinery (3) translocon clogging (4) ribosome stalling. Using model substrates and mutants, we showed it is activated by ribosome stalling! 5/8
Interestingly C53 forms a complex with UFL1, the E3 ligase that mediates #ufmylation and its adaptor DDRGK1. C53-UFL1-DDRGK1 complex is essential for ER stress tolerance, but not starvation. Same is true for all #ufmylation cascade 6/8
C53 directly binds #UFM1 and #ATG8 During ER stress UFM1 is depleted, exposing the sAIMs for ATG8 binding. Our story has parallels and differences with @amosliang2 and @jcornlab recent story on #ufmylation and #ER_phagy sciencedirect.com/science/articl… 7/8
Huge kudos to M. Stephani and L. Picchianti; the two @TrainingVbc students and all the colleagues who contributed. This is truly a @viennabiocenter story, with all 4 institutes and core facilities contributing. wouldn't be possible w/o them. 8/8
