Arp2/3 complex–dependent actin networks constrain myosin II function in driving retrograde actin flow

• Published in: The Journal of cell biology Vol. 197; no. 7; pp. 939 - 956
• Main Authors: Yang, Qing, Zhang, Xiao-Feng, Pollard, Thomas D., Forscher, Paul
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 25.06.2012; The Rockefeller University Press
• Subjects: Actin-Related Protein 2-3 Complex - metabolism; Actins - metabolism; Actins - ultrastructure; Animals; Aplysia - metabolism; Aplysia - ultrastructure; Cells; Flow rates; Growth Cones - metabolism; Growth Cones - ultrastructure; Kinases; Microscopy, Electron; Molecules; Motility; Myosin Type II - metabolism; Proteins; Translocation
• ISSN: 0021-9525; 1540-8140; 1540-8140
• DOI: 10.1083/jcb.201111052

The Arp2/3 complex nucleates actin filaments to generate networks at the leading edge of motile cells. Nonmuscle myosin II produces contractile forces involved in driving actin network translocation. We inhibited the Arp2/3 complex and/or myosin II with small molecules to investigate their respective functions in neuronal growth cone actin dynamics. Inhibition of the Arp2/3 complex with CK666 reduced barbed end actin assembly site density at the leading edge, disrupted actin veils, and resulted in veil retraction. Strikingly, retrograde actin flow rates increased with Arp2/3 complex inhibition; however, when myosin II activity was blocked, Arp2/3 complex inhibition now resulted in slowing of retrograde actin flow and veils no longer retracted. Retrograde flow rate increases induced by Arp2/3 complex inhibition were independent of Rho kinase activity. These results provide evidence that, although the Arp2/3 complex and myosin II are spatially segregated, actin networks assembled by the Arp2/3 complex can restrict myosin II–dependent contractility with consequent effects on growth cone motility.