title: The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1.
abstract: The small GTPase ADP-ribosylation factor 1 (ARF1) is a key regulator of intracellular membrane traffic. Regulators of ARF1, its GTPase-activating protein (GAP) and its guanine nucleotide exchange factor have been identified recently. However, it remains uncertain whether these regulators drive the GTPase cycle of ARF1 autonomously or whether their activities can be regulated by other proteins. Here, we demonstrate that the intracellular KDEL receptor, ERD2, self-oligomerizes and interacts with ARF1 GAP, and thereby regulates the recruitment of cytosolic ARF1 GAP to membranes. Because ERD2 overexpression enhances the recruitment of GAP to membranes and results in a phenotype that reflects ARF1 inactivation, our findings suggest that ERD2 regulates ARF1 GAP, and thus regulates ARF1-mediated transport.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Aoe
authors.forename: E
authors.initials: E
authors.lastname: Cukierman
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Cassel
authors.forename: P J
authors.initials: PJ
authors.lastname: Peters
authors.forename: V W
authors.initials: VW
authors.lastname: Hsu
mesh_terms: D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D019556:COS Cells; D017931:DNA Primers; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism*; D018000:Receptors, Peptide; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D020690:GTPase-Activating Proteins; C064459:KDEL receptor; C489304:KDELR1 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011506:Proteins; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors