Cortactin promotes cell motility by enhancing lamellipodial persistence.

Bryce NS, Clark ES, Leysath JL, Currie JD, Webb DJ, Weaver AM
Curr Biol. 2005 15 (14): 1276-85

PMID: 16051170 · DOI:10.1016/j.cub.2005.06.043

BACKGROUND - Lamellipodial protrusion, which is the first step in cell movement, is driven by actin assembly and requires activity of the Arp2/3 actin-nucleating complex. However, it is unclear how actin assembly is dynamically regulated to support effective cell migration.

RESULTS - Cells deficient in cortactin have impaired cell migration and invasion. Kymography analyses of live-cell imaging studies demonstrate that cortactin-knockdown cells have a selective defect in the persistence of lamellipodial protrusions. The motility and protrusion defects are fully rescued by cortactin molecules, provided both the Arp2/3 complex and F-actin binding sites are intact. Consistent with this requirement for simultaneous contacts with Arp2/3 and F-actin, cortactin is recruited by Arp2/3 complex to lamellipodia and binds with a higher affinity to ATP/ADP-Pi-F-actin than to ADP-F-actin. In situ labeling of lamellipodia revealed that the relative levels of free barbed ends of actin filaments are reduced by over 30% in the cortactin-knockdown cells; however, there is no change in Arp2/3-complex localization to lamellipodia. Cortactin-knockdown cells also have a selective defect in the assembly of new adhesions in protrusions, as assessed by analysis of GFP-paxillin dynamics in living cells.

CONCLUSIONS - Cortactin enhances lamellipodial persistence, at least in part through regulation of Arp2/3 complex. The presence of cortactin also enhances the rate of new adhesion formation in lamellipodia. In vivo, these functions may be important during directed cell motility.

MeSH Terms (17)

Actin-Related Protein 2 Actin-Related Protein 3 Actins Adenosine Diphosphate Adenosine Triphosphate Base Sequence Blotting, Western Cell Line Cell Movement Cortactin Cytoskeletal Proteins Humans Kymography Microfilament Proteins Microscopy, Fluorescence Protein Binding Pseudopodia

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