title: Inhibitory signalling to the Arp2/3 complex steers cell migration.
abstract: Cell migration requires the generation of branched actin networks that power the protrusion of the plasma membrane in lamellipodia. The actin-related proteins 2 and 3 (Arp2/3) complex is the molecular machine that nucleates these branched actin networks. This machine is activated at the leading edge of migrating cells by Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein (WAVE, also known as SCAR). The WAVE complex is itself directly activated by the small GTPase Rac, which induces lamellipodia. However, how cells regulate the directionality of migration is poorly understood. Here we identify a new protein, Arpin, that inhibits the Arp2/3 complex in vitro, and show that Rac signalling recruits and activates Arpin at the lamellipodial tip, like WAVE. Consistently, after depletion of the inhibitory Arpin, lamellipodia protrude faster and cells migrate faster. A major role of this inhibitory circuit, however, is to control directional persistence of migration. Indeed, Arpin depletion in both mammalian cells and Dictyostelium discoideum amoeba resulted in straighter trajectories, whereas Arpin microinjection in fish keratocytes, one of the most persistent systems of cell migration, induced these cells to turn. The coexistence of the Rac-Arpin-Arp2/3 inhibitory circuit with the Rac-WAVE-Arp2/3 activatory circuit can account for this conserved role of Arpin in steering cell migration.
authors.affiliation: 1] Group Cytoskeleton in Cell Morphogenesis, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Gif-sur-Yvette 91190, France [2].
authors.forename: Irene
authors.initials: I
authors.lastname: Dang
authors.forename: Roman
authors.initials: R
authors.lastname: Gorelik
authors.forename: Carla
authors.initials: C
authors.lastname: Sousa-Blin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Derivery
authors.forename: Christophe
authors.initials: C
authors.lastname: Guérin
authors.forename: Joern
authors.initials: J
authors.lastname: Linkner
authors.forename: Maria
authors.initials: M
authors.lastname: Nemethova
authors.forename: Julien G
authors.initials: JG
authors.lastname: Dumortier
authors.forename: Florence A
authors.initials: FA
authors.lastname: Giger
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Chipysheva
authors.forename: Valeria D
authors.initials: VD
authors.lastname: Ermilova
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: Valérie
authors.initials: V
authors.lastname: Campanacci
authors.forename: Isaline
authors.initials: I
authors.lastname: Herrada
authors.forename: Anne-Gaelle
authors.initials: AG
authors.lastname: Planson
authors.forename: Susan
authors.initials: S
authors.lastname: Fetics
authors.forename: Véronique
authors.initials: V
authors.lastname: Henriot
authors.forename: Violaine
authors.initials: V
authors.lastname: David
authors.forename: Ksenia
authors.initials: K
authors.lastname: Oguievetskaia
authors.forename: Goran
authors.initials: G
authors.lastname: Lakisic
authors.forename: Fabienne
authors.initials: F
authors.lastname: Pierre
authors.forename: Anika
authors.initials: A
authors.lastname: Steffen
authors.forename: Adeline
authors.initials: A
authors.lastname: Boyreau
authors.forename: Nadine
authors.initials: N
authors.lastname: Peyriéras
authors.forename: Klemens
authors.initials: K
authors.lastname: Rottner
authors.forename: Sophie
authors.initials: S
authors.lastname: Zinn-Justin
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cherfils
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Antonina Y
authors.initials: AY
authors.lastname: Alexandrova
authors.forename: Nicolas B
authors.initials: NB
authors.lastname: David
authors.forename: J Victor
authors.initials: JV
authors.lastname: Small
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.forename: Laurent
authors.initials: L
authors.lastname: Blanchoin
authors.forename: Alexis
authors.initials: A
authors.lastname: Gautreau
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D002352:Carrier Proteins; D011506:Proteins; C000604273:arpin protein, human; D051057:Proto-Oncogene Proteins c-akt