Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Cytoskeleton | Bioinformatic
Cell migration requires the generation of branched actin networks that power the
protrusion of the plasma membrane in lamellipodia1, 2. The actin-related
proteins 2 and 3 (Arp2/3) complex is the molecular machine that nucleates these
branched actin networks3. 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 lamellipodia4,
5, 6. 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.
I, Gorelik R, Sousa-Blin C, Derivery E, Guérin C, Linkner J, Nemethova
M, Dumortier JG, Giger FA, Tchipysheva T, Ermilova V, Vacher S,
Campanacci V, Herrada I, Planson AG, Fetics S, Henriot V, David V,
Oguievetskaia K, Lakisic G, Pierre F, Steffen A, Boyreau A, Peyriéras N,
Rottner K, Zinn-Justin S, Cherfils J, Bièche I, Alexandrova A, David
NB, Small JV, Faix J, Blanchoin L, Gautreau A. (2013). Inhibitory
signalling to the Arp2/3 complex steers cell migration. Nature (Sous
Inhibitory signalling to the Arp2/3 complex steers cell migration.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.