
USP8はRabex5との相互作用によりRab5陽性の小胞に動員され、Rabex5の内分泌小胞からの解離と同時にRab7のGEFであるSAND-1/Mon1の動員を促進することで、内分泌小胞の成熟を制御する。


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The spatiotemporal transition of small GTPase Rab5 to Rab7 is crucial for early-to-late endosome maturation, yet the precise mechanism governing Rab5-to-Rab7 switching remains elusive. USP8, a ubiquitin-specific protease, plays a prominent role in the endosomal sorting of a wide range of transmembrane receptors and is a promising target in cancer therapy. Here, we identified that USP8 is recruited to Rab5-positive carriers by Rabex5, a guanine nucleotide exchange factor (GEF) for Rab5. The recruitment of USP8 dissociates Rabex5 from early endosomes (EEs) and meanwhile promotes the recruitment of the Rab7 GEF SAND-1/Mon1. In USP8-deficient cells, the level of active Rab5 is increased, while the Rab7 signal is decreased. As a result, enlarged EEs with abundant intraluminal vesicles (ILVs) accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.

### Competing Interest Statement

The authors have declared no competing interest.

Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation

内分泌細胞における時空間的なユビキチン特異的プロテアーゼusp8の動員が内分泌小胞の成熟を指示する


内分泌細胞における時空間的なユビキチン特異的プロテアーゼUSP8の動員が内分泌小胞の成熟を指示する
