AI Article Synopsis
- The transition from small GTPase Rab5 to Rab7 is vital for endosome maturation, but how this switch happens is not fully understood.
- USP8, a deubiquitinating enzyme, is recruited to Rab5-positive carriers by Rabex5, impacting the endosome sorting of various receptors.
- In cells lacking USP8, there is increased active Rab5 but decreased Rab7 signals, leading to enlarged early endosomes and poorly developed lysosomes, highlighting USP8's key role in this process.
Article Abstract
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 accumulate and digestive lysosomes are rudimentary. Together, our results reveal an important and unexpected role of a deubiquitinating enzyme in endosome maturation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584181 | PMC |
| http://dx.doi.org/10.7554/eLife.96353 | DOI Listing |
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