title: The Arp2/3 activators WAVE and WASP have distinct genetic interactions with Rac GTPases in Caenorhabditis elegans axon guidance.
abstract: In the developing nervous system, axons are guided to their targets by the growth cone. Lamellipodial and filopodial protrusions from the growth cone underlie motility and guidance. Many molecules that control lamellipodia and filopodia formation, actin organization, and axon guidance have been identified, but it remains unclear how these molecules act together to control these events. Experiments are described here that indicate that, in Caenorhabditis elegans, two WH2-domain-containing activators of the Arp2/3 complex, WVE-1/WAVE and WSP-1/WASP, act redundantly in axon guidance and that GEX-2/Sra-1 and GEX-3/Kette, molecules that control WAVE activity, might act in both pathways. WAVE activity is controlled by Rac GTPases, and data are presented here that suggest WVE-1/WAVE and CED-10/Rac act in parallel to a pathway containing WSP-1/WASP and MIG-2/RhoG. Furthermore, results here show that the CED-10/WVE-1 and MIG-2/WSP-1 pathways act in parallel to two other molecules known to control lamellipodia and filopodia and actin organization, UNC-115/abLIM and UNC-34/Enabled. These results indicate that at least three actin-modulating pathways act in parallel to control actin dynamics and lamellipodia and filopodia formation during axon guidance (WASP-WAVE, UNC-115/abLIM, and UNC-34/Enabled).
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045-7534, USA.
authors.forename: M Afaq
authors.initials: MA
authors.lastname: Shakir
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.forename: Eric C
authors.initials: EC
authors.lastname: Struckhoff
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Demarco
authors.forename: Falshruti B
authors.initials: FB
authors.lastname: Patel
authors.forename: Martha C
authors.initials: MC
authors.lastname: Soto
authors.forename: Erik A
authors.initials: EA
authors.lastname: Lundquist
mesh_terms: D051377:Actin-Related Protein 2 / Q000235:genetics / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051377:Actin-Related Protein 2; D051376:Actin-Related Protein 2-3 Complex; D051378:Actin-Related Protein 3; C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C450821:GEX-2 protein, C elegans; C450822:GEX-3 protein, C elegans; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C472306:UNC-115 protein, C elegans; C476569:arx-1 protein, C elegans; C476568:arx-2 protein, C elegans; C511070:unc-34 protein, C elegans; C532812:wsp-1 protein, C elegans; C532811:wve-1 protein, C elegans; C442327:Mig-2 protein, C elegans; D020744:rac GTP-Binding Proteins