title: ARFGAP1 promotes AP-2-dependent endocytosis.
abstract: COPI (coat protein I) and the clathrin-AP-2 (adaptor protein 2) complex are well-characterized coat proteins, but a component that is common to these two coats has not been identified. The GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1), ARFGAP1, is a known component of the COPI complex. Here, we show 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 coat proteins leads to selective inhibition in the corresponding transport pathway. The role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Bai
authors.forename: Helge
authors.initials: H
authors.lastname: Gad
authors.forename: Gabriele
authors.initials: G
authors.lastname: Turacchio
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cocucci
authors.forename: Jia-Shu
authors.initials: JS
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Galina V
authors.initials: GV
authors.lastname: Beznoussenko
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie
authors.forename: Ruibai
authors.initials: R
authors.lastname: Luo
authors.forename: Lianwu
authors.initials: L
authors.lastname: Fu
authors.forename: James F
authors.initials: JF
authors.lastname: Collawn
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhausen
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Victor W
authors.initials: VW
authors.lastname: Hsu
mesh_terms: D004705:Endocytosis / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000502:physiology*; D006801:Humans; D008854:Microscopy, Electron; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism / Q000502:physiology*
chemical_list: C503237:ARFGAP1 protein, human; D020690:GTPase-Activating Proteins; D011990:Receptors, Transferrin; D050656:Transcription Factor AP-2