ACAP1 promotes endocytic recycling by recognizing recycling sorting signals.

Cargo sorting that promotes the transport of cargo proteins from a membrane compartment has been predicted to be unlikely in the endocytic recycling pathways. We now show that ACAP1 binds specifically and directly to recycling cargo proteins. Reducing this interaction for TfR inhibits its recycling. Moreover, ACAP1 binds to two distinct phenylalanine-based sequences in the cytoplasmic domain of TfR that function as recycling sorting signals to promote its transport from the recycling endosome. Taken together, these findings indicate that ACAP1 promotes cargo sorting by recognizing recycling sorting signals.