Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor

摘要: Clathrin-coated pits at the cell surface select material for transportation into interior. A major mode of cargo selection bud site is via μ2 subunit AP-2 adaptor complex, which recognizes tyrosine-based internalization signals. Other motifs and signals, including phosphorylation ubiquitylation, also tag certain proteins incorporation a coated vesicle, but mechanism unclear. Disabled-2 (Dab2) FXNPXY motif in LDL-receptor family members an N-terminal phosphotyrosine-binding (PTB) domain. Here, we show that addition to binding AP-2, Dab2 binds directly phosphoinositides clathrin, assembling triskelia regular polyhedral coats. The contact different regions PTB domain, can stably anchor membrane surface, while distal clathrin-binding determinants regulate clathrin lattice assembly. We propose typical member growing cargo-specific proteins, β-arrestin, AP180, epsin, HIP1 numb, clathrin-coat assembly plasma by synchronizing polymerization events.