细胞迁移由分岔的肌动蛋白网络驱动,后者由Arp2/3复合物的成核活动产生。在这项研究中,Alexis Gautreau及同事识别出一个新蛋白,叫做Arpin,它抑制Arp2/3复合物,通过降低细胞速度和迁移的方向持久性限制细胞乱动。
因此,Arpin引导细胞迁移,是对受各种提示信息影响而发生偏颇的无数生理性迁移活动进行微调的首要目标。(生物谷Bioon.com)
生物谷推荐的英文摘要
Nature doi:10.1038/nature12611
Inhibitory signalling to the Arp2/3 complex steers cell migration
Irene Dang,Roman Gorelik,Carla Sousa-Blin,EmmanuelDerivery,Christophe Guerin,Joern Linkner,Maria Nemethova,Julien G. Dumortier,Florence A. Giger,Tamara A. Chipysheva,Valeria D. Ermilova,Sophie Vacher,Valerie Campanacci,Isaline Herrada,Anne-Gaelle Planson,Susan Fetics,Veronique Henriot,Violaine David,Ksenia Oguievetskaia,Goran Lakisic,Fabienne Pierre,Anika Steffen,Adeline Boyreau,Nadine Peyrieras,Klemens Rottner
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.