title: Enabled negatively regulates diaphanous-driven actin dynamics in vitro and in vivo.
abstract: Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Bilancia
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Winkelman
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Tsygankov
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Nowotarski
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sees
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Comber
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Iwan
authors.initials: I
authors.lastname: Evans
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Vinal
authors.initials: V
authors.lastname: Lakhani
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: Will
authors.initials: W
authors.lastname: Wood
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Elston
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.affiliation: Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: peifer@unc.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Peifer
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D000080865:Formins; D006434:Hemocytes / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C092744:ENA-VASP proteins; D000080865:Formins; C106890:diaphanous protein, Drosophila