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

Sanjay K Mishra, Peter Keyel, Matthew J Hawryluk, Nicole R Agostinelli, Simon C Watkins, Linton M Traub

Research output: Contribution to journalArticle


Clathrin-coated pits at the cell surface select material for transportation into the cell interior. A major mode of cargo selection at the bud site is via the μ2 subunit of the AP-2 adaptor complex, which recognizes tyrosine-based internalization signals. Other internalization motifs and signals, including phosphorylation and ubiquitylation, also tag certain proteins for incorporation into a coated vesicle, but the mechanism of selection is unclear. Disabled-2 (Dab2) recognizes the FXNPXY internalization motif in LDL-receptor family members via an N-terminal phosphotyrosine-binding (PTB) domain. Here, we show that in addition to binding AP-2, Dab2 also binds directly to phosphoinositides and to clathrin, assembling triskelia into regular polyhedral coats. The FXNPXY motif and phosphoinositides contact different regions of the PTB domain, but can stably anchor Dab2 to the membrane surface, while the distal AP-2 and clathrin-binding determinants regulate clathrin lattice assembly. We pr
Original languageEnglish
Pages (from-to)4915-4926
JournalEMBO Journal
StatePublished - 2002


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