PUBLICATION

Inhibitory signalling to the Arp2/3 complex steers cell migration.

Authors
Dang, I., Gorelik, R., Sousa-Blin, C., Derivery, E., Guérin, C., Linkner, J., Nemethova, M., Dumortier, J.G., Giger, F.A., Chipysheva, T.A., Ermilova, V.D., Vacher, S., Campanacci, V., Herrada, I., Planson, A.G., 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.Y., David, N.B., Small, J.V., Faix, J., Blanchoin, L., Gautreau, A.
ID
ZDB-PUB-170525-5
Date
2013
Source
Nature   503(7475): 281-4 (Journal)
Registered Authors
Peyriéras, Nadine
Keywords
none
MeSH Terms
  • Cell Line
  • Humans
  • Cell Movement/genetics*
  • Actin-Related Protein 2-3 Complex/metabolism*
  • Zebrafish/genetics
  • Dictyostelium/genetics
  • Dictyostelium/metabolism
  • Pseudopodia/genetics*
  • Pseudopodia/metabolism*
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism
  • Embryo, Nonmammalian
  • Mice
  • Animals
  • Proteins/genetics
  • Proteins/metabolism
  • HEK293 Cells
  • Gene Knockout Techniques
  • Signal Transduction*
  • Proto-Oncogene Proteins c-akt/metabolism
(all 20)
PubMed
24132237 Full text @ Nature
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.

Genes / Markers
Figures
No images available
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ml1TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Fish
    1 - 3 of 3
    Show
    Antibodies
    No data available
    Orthology
    Gene Orthology
    arpin
    1 - 1 of 1
    Show
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
    1 - 1 of 1
    Show
    Mapping
    No data available