A ROLE FOR POR1, A RAC1-INTERACTING PROTEIN, IN ARF6-MEDIATED CYTOSKELETAL REARRANGEMENTS

The ARF6 GTPase, the least conserved member of the ADP ribosylation fa ctor (ARF) family, associates,vith the plasma membrane and intracellul ar endosome vesicles, Mutants of ARF6 defective in GTP binding and hyd rolysis have a marked effect on endocytic trafficking and the gross mo rphology of the peripheral membrane system, Here we report that expres sion of the GTPase-defective mutant of ARF6, ARF6(Q67L), remodels the actin cytoskeleton by inducing actin polymerization at the cell periph ery, 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,vith the dominant-negative muta nt of Rad, Rac1(S17N), A synergistic effect between POR1 and ARF6 for the induction of actin polymerization was detected, Furthermore, we ob served that ARF6 interacts directly with POR1 and that this interactio n was GTP dependent, These findings indicate that ARF6 and Rad functio n on distinct signaling pathways to mediate cytoskeletal reorganizatio n, and suggest a role for POR1 as an important regulatory element in o rchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1.