Back

The Rubicon-WIPI axis regulates exosome biogenesis during aging

Yanagawa, K.; Kuma, A.; Hamasaki, M.; Kita, S.; Yamamuro, T.; Nishino, K.; Nakamura, S.; Omori, H.; Kaminishi, T.; Oikawa, S.; Kato, Y.; Edahiro, R.; Kawagoe, R.; Taniguchi, T.; Tanaka, Y.; Shima, T.; Tabata, K.; Iwatani, M.; Bekku, N.; Hanayama, R.; Okada, Y.; Akimoto, T.; Kosako, H.; Takahashi, A.; Shimomura, I.; Sakata, Y.; Yoshimori, T.

2024-05-10 cell biology
10.1101/2024.05.08.593233 bioRxiv
Show abstract

Cells release intraluminal vesicles (ILVs) in multivesicular bodies as exosomes to communicate with other cells. Although recent studies suggest an intimate link between exosome biogenesis and autophagy, the detailed mechanism is not fully understood. Here we employed comprehensive RNAi screening for autophagy-related factors and discovered that Rubicon, a negative regulator of autophagy, is essential for exosome release. Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Interactome analysis of WIPI2d identified the ESCRT components that are required for ILV formation. Notably, we found that Rubicon is required for an age-dependent increase of exosome release in mice. In addition, small RNA sequencing of serum exosomes revealed that Rubicon determines the fate of exosomal microRNAs associated with cellular senescence and longevity pathways. Taken together, our current results suggest that the Rubicon-WIPI axis functions as a key regulator of exosome biogenesis and is responsible for the age-dependent changes in exosome quantity and quality.

Matching journals

The top 6 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.