ARFGAP1 promotes endocytosis regulated by AP-2

Two of the best characterized coat proteins are Coat Protein (COP) I and clathrin associated with Adaptor Protein 2 (AP-2), for which no common component has been identified. A GTPase-activating protein (GAP) for ADP-Ribosylation Factor 1 (ARF1), ARFGAP1, is known to act as a component of the COPI complex. Here, we find that distinct regions of ARFGAP1 interact with AP-2 and coatomer (components of the COPI complex). Selectively disrupting the interaction of ARFGAP1 with either of these two coats leads to selective inhibition in the corresponding transport pathway. Elucidating how ARFGAP1 acts in endocytosis regulated by AP-2, we find mechanistic parallels to its elucidated roles in COPI transport, as both its GAP activity and its coat function contribute to promoting AP-2 transport.