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

J Cell Biol. 2012 Jun 25;197(7):939-56. doi: 10.1083/jcb.201111052. Epub 2012 Jun 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins / metabolism*
  • Actins / ultrastructure
  • Animals
  • Aplysia / metabolism*
  • Aplysia / ultrastructure
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Microscopy, Electron
  • Myosin Type II / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Myosin Type II