title: A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements.
abstract: The ARF6 GTPase, the least conserved member of the ADP ribosylation factor (ARF) family, associates with the plasma membrane and intracellular endosome vesicles. Mutants of ARF6 defective in GTP binding and hydrolysis have a marked effect on endocytic trafficking and the gross morphology of the peripheral membrane system. Here we report that expression of the GTPase-defective mutant of ARF6, ARF6(Q67L), remodels the actin cytoskeleton by inducing actin polymerization at the cell periphery. This cytoskeletal rearrangement was inhibited by co-expression of ARF6(Q67L) with deletion mutants of POR1, a Rac1-interacting protein involved in membrane ruffling, but not with the dominant-negative mutant of Rac1, Rac1(S17N). A synergistic effect between POR1 and ARF6 for the induction of actin polymerization was detected. Furthermore, we observed that ARF6 interacts directly with POR1 and that this interaction was GTP dependent. These findings indicate that ARF6 and Rac1 function on distinct signaling pathways to mediate cytoskeletal reorganization, and suggest a role for POR1 as an important regulatory element in orchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1.
authors.affiliation: Department of Cell Biology, Washington University School of Medicine, Box 8228, 660 South Euclid Ave, St Louis, MO 63110, USA. schorey@cellbio.wustl.edu
authors.forename: C
authors.initials: C
authors.lastname: D'Souza-Schorey
authors.forename: R L
authors.initials: RL
authors.lastname: Boshans
authors.forename: M
authors.initials: M
authors.lastname: McDonough
authors.forename: P D
authors.initials: PD
authors.lastname: Stahl
authors.forename: L
authors.initials: L
authors.lastname: Van Aelst
mesh_terms: D020727:ADP-Ribosylation Factors; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins
chemical_list: C101158:ARFIP2 protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D020744:rac GTP-Binding Proteins