title: GMF promotes leading-edge dynamics and collective cell migration in vivo.
abstract: Lamellipodia are dynamic actin-rich cellular extensions that drive advancement of the leading edge during cell migration. Lamellipodia undergo periodic extension and retraction cycles, but the molecular mechanisms underlying these dynamics and their role in cell migration have remained obscure. We show that glia-maturation factor (GMF), which is an Arp2/3 complex inhibitor and actin filament debranching factor, regulates lamellipodial protrusion dynamics in living cells. In cultured S2R(+) cells, GMF silencing resulted in an increase in the width of lamellipodial actin filament arrays. Importantly, live-cell imaging of mutant Drosophila egg chambers revealed that the dynamics of actin-rich protrusions in migrating border cells is diminished in the absence of GMF. Consequently, velocity of border cell clusters undergoing guided migration was reduced in GMF mutant flies. Furthermore, genetic studies demonstrated that GMF cooperates with the Drosophila homolog of Aip1 (flare) in promoting disassembly of Arp2/3-nucleated actin filament networks and driving border cell migration. These data suggest that GMF functions in vivo to promote the disassembly of Arp2/3-nucleated actin filament arrays, making an important contribution to cell migration within a 3D tissue environment.
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Poukkula
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Hakala
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
authors.forename: Nalle
authors.initials: N
authors.lastname: Pentinmikko
authors.affiliation: Rosenstiel Center for Basic Biomedical Research, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Meredith O
authors.initials: MO
authors.lastname: Sweeney
authors.affiliation: Rosenstiel Center for Basic Biomedical Research, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Jansen
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland; Department of Biosciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Mattila
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland; Department of Biosciences, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Hietakangas
authors.affiliation: Rosenstiel Center for Basic Biomedical Research, Brandeis University, Waltham, MA 02453, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Goode
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. Electronic address: pekka.lappalainen@helsinki.fi.
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000378:metabolism; D020904:Glia Maturation Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D011554:Pseudopodia / Q000502:physiology* / Q000648:ultrastructure
chemical_list: C511870:ALIX protein, Drosophila; D051376:Actin-Related Protein 2-3 Complex; D029721:Drosophila Proteins; D020904:Glia Maturation Factor; D008840:Microfilament Proteins