TY - JOUR
T1 - GMF promotes leading-edge dynamics and collective cell migration in vivo
AU - Poukkula, Minna
AU - Hakala, Markku
AU - Pentinmikko, Nalle
AU - Sweeney, Meredith O.
AU - Jansen, Silvia
AU - Mattila, Jaakko
AU - Hietakangas, Ville
AU - Goode, Bruce L.
AU - Lappalainen, Pekka
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/11/3
Y1 - 2014/11/3
N2 - Summary Lamellipodia are dynamic actin-rich cellular extensions that drive advancement of the leading edge during cell migration [1-3]. Lamellipodia undergo periodic extension and retraction cycles [4-8], 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 [9, 10], 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.
AB - Summary Lamellipodia are dynamic actin-rich cellular extensions that drive advancement of the leading edge during cell migration [1-3]. Lamellipodia undergo periodic extension and retraction cycles [4-8], 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 [9, 10], 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.
UR - http://www.scopus.com/inward/record.url?scp=84914171011&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2014.08.066
DO - 10.1016/j.cub.2014.08.066
M3 - Article
C2 - 25308079
AN - SCOPUS:84914171011
SN - 0960-9822
VL - 24
SP - 2533
EP - 2540
JO - Current Biology
JF - Current Biology
IS - 21
ER -