title: Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton.
abstract: Ena/VASP proteins and the WAVE regulatory complex (WRC) regulate cell motility by virtue of their ability to independently promote actin polymerization. We demonstrate that Ena/VASP and the WRC control actin polymerization in a cooperative manner through the interaction of the Ena/VASP EVH1 domain with an extended proline rich motif in Abi. This interaction increases cell migration and enables VASP to cooperatively enhance WRC stimulation of Arp2/3 complex-mediated actin assembly in vitro in the presence of Rac. Loss of this interaction in Drosophila macrophages results in defects in lamellipodia formation, cell spreading, and redistribution of Ena to the tips of filopodia-like extensions. Rescue experiments of abi mutants also reveals a physiological requirement for the Abi:Ena interaction in photoreceptor axon targeting and oogenesis. Our data demonstrate that the activities of Ena/VASP and the WRC are intimately linked to ensure optimal control of actin polymerization during cell migration and development.
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Xing Judy
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Institute of Neurobiology, University of Muenster, Badestrasse 9, 48149 Muenster, Germany.
authors.forename: Anna Julia
authors.initials: AJ
authors.lastname: Squarr
authors.affiliation: Institute of Neurobiology, University of Muenster, Badestrasse 9, 48149 Muenster, Germany.
authors.forename: Raiko
authors.initials: R
authors.lastname: Stephan
authors.affiliation: Howard Hughes Medical Institute and Department of Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Chen
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Higgins
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Barry
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Morag C
authors.initials: MC
authors.lastname: Martin
authors.affiliation: Howard Hughes Medical Institute and Department of Biophysics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Rosen
authors.affiliation: Institute of Neurobiology, University of Muenster, Badestrasse 9, 48149 Muenster, Germany. Electronic address: sbogdan@uni-muenster.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
authors.affiliation: Cell Motility Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: michael.way@cancer.org.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Way
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; D011392:Proline