Cortactin Promotes Migration and Platelet-derived Growth Factor-induced Actin Reorganization by Signaling to Rho-GTPases
- 15 July 2009
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 20 (14), 3209-3223
- https://doi.org/10.1091/mbc.e08-12-1180
Abstract
Dynamic actin rearrangements are initiated and maintained by actin filament nucleators, including the Arp2/3-complex. This protein assembly is activated in vitro by distinct nucleation-promoting factors such as Wiskott-Aldrich syndrome protein/Scar family proteins or cortactin, but the relative in vivo functions of each of them remain controversial. Here, we report the conditional genetic disruption of murine cortactin, implicated previously in dynamic actin reorganizations driving lamellipodium protrusion and endocytosis. Unexpectedly, cortactin-deficient cells showed little changes in overall cell morphology and growth. Ultrastructural analyses and live-cell imaging studies revealed unimpaired lamellipodial architecture, Rac-induced protrusion, and actin network turnover, although actin assembly rates in the lamellipodium were modestly increased. In contrast, platelet-derived growth factor-induced actin reorganization and Rac activation were impaired in cortactin null cells. In addition, cortactin deficiency caused reduction of Cdc42 activity and defects in random and directed cell migration. Reduced migration of cortactin null cells could be restored, at least in part, by active Rac and Cdc42 variants. Finally, cortactin removal did not affect the efficiency of receptor-mediated endocytosis. Together, we conclude that cortactin is fully dispensable for Arp2/3-complex activation during lamellipodia protrusion or clathrin pit endocytosis. Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases.Keywords
This publication has 81 references indexed in Scilit:
- p53-cofactor JMY is a multifunctional actin nucleation factorNature, 2009
- Arp2 depletion inhibits sheet‐like protrusions but not linear protrusions of fibroblasts and lymphocytesCell Motility, 2008
- WHAMM Is an Arp2/3 Complex Activator That Binds Microtubules and Functions in ER to Golgi TransportCell, 2008
- Cortactin branches out: Roles in regulating protrusive actin dynamicsCell Motility, 2008
- Differently phosphorylated forms of the cortactin homolog HS1 mediate distinct functions in natural killer cellsNature Immunology, 2008
- Arp2/3 complex interactions and actin network turnover in lamellipodiaThe EMBO Journal, 2008
- Collagen loss and impaired wound healing is associated with c-Myb deficiencyThe Journal of Pathology, 2007
- The ARP2/3 complex: an actin nucleator comes of ageNature Reviews Molecular Cell Biology, 2006
- HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune SynapseImmunity, 2006
- Cortactin Promotes Cell Motility by Enhancing Lamellipodial PersistenceCurrent Biology, 2005