K-29 linked ubiquitination of Arrdc4 regulates its function in extracellular vesicle biogenesis.

ABSTRACT: Extracellular vesicles (EVs) are important mediators of intercellular communication. However, EV biogenesis remains poorly understood. We previously defined a role for Arrdc4 (Arrestin domain containing protein 4), an adaptor for Nedd4 family ubiquitin ligases, in the biogenesis of EVs. Here we report that ubiquitination of Arrdc4 is critical for its role in EV secretion. We identified five potential ubiquitinated lysine residues in Arrdc4 using mass spectrometry. By analysing Arrdc4 lysine mutants we discovered that lysine 270 (K270) is critical for Arrdc4 function in EV biogenesis. Arrdc4^K270R mutation caused a decrease in the number of EVs released by cells compared to Arrdc4^WT , and a reduction in trafficking of divalent metal transporter (DMT1) into EVs. Furtherm

SUBMITTER: Farooq AU 

PROVIDER: S-EPMC8807422 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature