Arp2/3 complex nucleates branched actin networks that drive cell motility and intracellular trafficking. Coronins, a family of seven proteins in humans, inhibit Arp2/3 complex in vitro and reduce branch density in cells. Coro7, a distant member of this family, features two β-propeller domains (β1β2) and C-terminal Central-Acidic (CA) domains and remains poorly studied. Here, cryo-EM and biochemical data show that CA binds subunit Arp3 of free Arp2/3 complex with ~1 µM affinity, inhibiting polymerization like Arpin, while displacing Arp3's autoinhibitory C-terminal tail and promoting the active, short-pitch conformation, like WASP-family nucleation-promoting factors. Full-length Coro7, however, does not inhibit Arp2/3 complex polymerization but effectively induces debranching, whereas the isolated β1β2 or CA domains do not. In cells, Coro7 depletion disrupts ER-Golgi transport, which is rescued by full-length Coro7 but not by truncated variants. These results suggest that Coro7 functions as an Arp2/3 complex branch disassembly factor implicated in actin-dependent ER-Golgi trafficking.
© 2025. The Author(s).