title: Rab1 recruits WHAMM during membrane remodeling but limits actin nucleation.
abstract: Small G-proteins are key regulatory molecules that activate the actin nucleation machinery to drive cytoskeletal rearrangements during plasma membrane remodeling. However, the ability of small G-proteins to interact with nucleation factors on internal membranes to control trafficking processes has not been well characterized. Here we investigated roles for members of the Rho, Arf, and Rab G-protein families in regulating WASP homologue associated with actin, membranes, and microtubules (WHAMM), an activator of Arp2/3 complex-mediated actin nucleation. We found that Rab1 stimulated the formation and elongation of WHAMM-associated membrane tubules in cells. Active Rab1 recruited WHAMM to dynamic tubulovesicular structures in fibroblasts, and an active prenylated version of Rab1 bound directly to an N-terminal domain of WHAMM in vitro. In contrast to other G-protein-nucleation factor interactions, Rab1 binding inhibited WHAMM-mediated actin assembly. This ability of Rab1 to regulate WHAMM and the Arp2/3 complex represents a distinct strategy for membrane remodeling in which a Rab G-protein recruits the actin nucleation machinery but dampens its activity.
authors.affiliation: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Russo
authors.affiliation: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269.
authors.forename: Alyssa J
authors.initials: AJ
authors.lastname: Mathiowetz
authors.affiliation: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269.
authors.forename: Steven
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Welch
authors.affiliation: Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269 kenneth.campellone@uconn.edu.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Campellone
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004285:Dogs; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C578123:WHAMM protein, human; D020691:rab GTP-Binding Proteins; D020741:rho GTP-Binding Proteins
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