ESCRT-0 condensation and cargo clustering drive extracellular vesicle budding from cilia.

ESCRT-0 condensation at the ciliary tip in mouse kidney cells clusters ubiquitinated Smoothened (SMO) and drives cilia-derived extracellular vesicle budding without ESCRT-III scission.

• Why it matters: Cargo selection for ciliary EVs is linked to ubiquitin chains, but how that selection is coupled to the physical budding step was unclear.
• What they did: In mouse kidney cells, the study tested ESCRT-0’s role in SMO packaging and EV biogenesis, including ESCRT-III dependence, ESCRT-0 condensation disruption, and optogenetic SMO clustering with forced ESCRT-0 recruitment.
• The result: Blocking ESCRT-0 condensation prevented SMO secretion, while combining forced ESCRT-0 recruitment with optogenetic SMO clustering reconstituted EV budding, supporting a minimal ESCRT-III-independent reverse-topology module.

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