title: ADP-ribosylation factor-like GTPase ARFRP1 is required for trans-Golgi to plasma membrane trafficking of E-cadherin.
abstract: ADP-ribosylation factor-related protein 1 (ARFRP1) plays a specific role in Golgi function controlling recruitment of GRIP domain proteins and ARL1 to the trans-Golgi. Deletion of the mouse Arfrp1 gene causes embryonic lethality during early gastrulation, because epiblast cells detach from the ectodermal cell layer and do not differentiate to mesodermal tissue. Here we show that in Arfrp1(-/-) embryos E-cadherin is mistargeted to intracellular compartments, whereas in control embryos it is present at the cell surface of trophectodermal and ectodermal cells. In enterocytes of intestine-specific Arfrp1 null mutants (Arfrp1(vil)(-/-)), E-cadherin is associated with intracellular membranes, partially colocalizing with the cis-Golgi marker GM130 or with punctae close to the cell surface. In contrast, in control enterocytes E-cadherin is exclusively located in the lateral membranes. In addition, ARL1 is dislocated from Golgi membranes to the cytosol of Arfrp1(vil)(-/-) enterocytes. Depletion of endogenous ARFRP1 by RNA interference leads to a dislocation of E-cadherin from the cell surface in HeLa cells and to a reduced cell aggregation in Ltk(-)Ecad cells. ARFRP1 was coimmunoprecipitated in a complex with E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and p120(ctn) from lysates of Madin-Darby canine kidney cells stably expressing myc-ARFRP1. These data indicate that knock-out of Arfrp1 disrupts the trafficking of E-cadherin through the Golgi and suggest an essential role of the GTPase in trans-Golgi network function.
authors.affiliation: Department of Pharmacology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Zahn
authors.forename: Alexander
authors.initials: A
authors.lastname: Jaschke
authors.forename: Jörg
authors.initials: J
authors.lastname: Weiske
authors.forename: Angela
authors.initials: A
authors.lastname: Hommel
authors.forename: Deike
authors.initials: D
authors.lastname: Hesse
authors.forename: Robert
authors.initials: R
authors.lastname: Augustin
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Simone
authors.initials: S
authors.lastname: Florian
authors.forename: Andrea
authors.initials: A
authors.lastname: Scheepers
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Otmar
authors.initials: O
authors.lastname: Huber
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004475:Ectoderm / Q000378:metabolism; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference
chemical_list: D015820:Cadherins; D051177:Catenins; D020727:ADP-Ribosylation Factors; C531986:Arfrp1 protein, mouse