Conserved N- and C-terminal motifs of PAD-1 are required to inhibit extracellular vesicle release

The Dopey family protein PAD-1 is a key regulator of extracellular vesicle (EV) release in Caenorhabditis elegans (Beer et al., 2018; Fazeli et al., 2020). PAD-1 is thought to inhibit EV release by activating the phospholipid flippase TAT-5 to maintain phosphatidylethanolamine (PE) asymmetry in the plasma membrane. When PAD-1 is disrupted, cytofacial PE is externalized, membrane-sculpting ESCRT complexes are recruited to the plasma membrane, and EVs bud from the plasma membrane by ectocytosis (Beer et al., 2018; Beer, 2021). However, which domains of PAD-1 are important to regulate EV release was unknown.