Cargo crosslinking nucleates AP-1 lattice formation.

Cargo molecules with tandem sorting motifs directly nucleate AP-1 lattice formation by bridging complexes, enhancing coat assembly and cargo trafficking in cells.

• Why it matters: Understanding how cargo influences coat assembly addresses a key gap in vesicle trafficking mechanisms, which are vital for proper protein and lipid distribution in eukaryotic cells.
• What they did: Cryo-EM structures of human AP-1 bound to cargo with tandem motifs at 3.5–4.0 Å resolution revealed a novel μ1-σ1 inter-complex interface that promotes adaptor oligomerization and coat formation.
• The result: This cargo-mediated nucleation mechanism improves AP-1-clathrin cage assembly and cargo trafficking, impacting neuronal development in zebrafish and expanding the understanding of vesicle formation regulation.