Back

Lysosomes dock to omegasomes and ER-connected Phagophores During DNAJB12 and GABARAP-Dependent Selective-Autophagy of Misfolded P23H-Rhodopsin

Kennedy, A. S.; Ren, H. Y.; Madden, V.; Cyr, D. M.

2021-10-20 cell biology
10.1101/2021.10.20.465144 bioRxiv
Show abstract

We report on how the ER-associated-autophagy pathway (ERAA) delivers P23H-rhodopsin (P23H-R) to the lysosome. P23H-R accumulates in an ERAD-resistant conformation that is stabilized by DNAJB12 and Hsp70. P23H-R, DNAJB12, and FIP200 co-localize in discrete foci that punctuate the rim of omegasome rings coated by WIPI1. P23H-R tubules thread through the wall of WIPI1 rings into their central cavity. Transfer of P23H-R from ER-connected phagophores to lysosomes requires GABARAP, and is associated with the transient docking of lysosomes to WIPI1 rings. Instances of lysosomes docking to WIPI1 foci are constitutive, and increase 250% upon P23H-R expression. After departure from WIPI1 rings, new patches of P23H-R are seen in the membranes of lysosomes. The absence of GABARAP prevents transfer of P23H-R from phagophores to lysosomes without interfering with docking. These data identify lysosome docking to omegasomes as an important step in the DNAJB12 and GABARAP-dependent autophagic disposal of dominantly toxic P23H-R.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.