Publication Date:
2013-10-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Irene -- Gorelik, Roman -- Sousa-Blin, Carla -- Derivery, Emmanuel -- Guerin, Christophe -- Linkner, Joern -- Nemethova, Maria -- Dumortier, Julien G -- Giger, Florence A -- Chipysheva, Tamara A -- Ermilova, Valeria D -- Vacher, Sophie -- Campanacci, Valerie -- Herrada, Isaline -- Planson, Anne-Gaelle -- Fetics, Susan -- Henriot, Veronique -- David, Violaine -- Oguievetskaia, Ksenia -- Lakisic, Goran -- Pierre, Fabienne -- Steffen, Anika -- Boyreau, Adeline -- Peyrieras, Nadine -- Rottner, Klemens -- Zinn-Justin, Sophie -- Cherfils, Jacqueline -- Bieche, Ivan -- Alexandrova, Antonina Y -- David, Nicolas B -- Small, J Victor -- Faix, Jan -- Blanchoin, Laurent -- Gautreau, Alexis -- England -- Nature. 2013 Nov 14;503(7475):281-4. doi: 10.1038/nature12611. Epub 2013 Oct 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Group Cytoskeleton in Cell Morphogenesis, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Gif-sur-Yvette 91190, France [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132237" target="_blank"〉PubMed〈/a〉
Keywords:
Actin-Related Protein 2-3 Complex/*metabolism
;
Animals
;
Carrier Proteins/genetics/metabolism
;
Cell Line
;
Cell Movement/*genetics
;
Dictyostelium/genetics/metabolism
;
Embryo, Nonmammalian
;
Gene Knockout Techniques
;
HEK293 Cells
;
Humans
;
Mice
;
Proteins/genetics/metabolism
;
Proto-Oncogene Proteins c-akt/metabolism
;
Pseudopodia/*genetics/*metabolism
;
*Signal Transduction
;
Zebrafish/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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