Two Functionally Distinct Sources of Actin Monomers Supply the Leading Edge of Lamellipodia

Cell Rep. 2015 Apr 21;11(3):433-45. doi: 10.1016/j.celrep.2015.03.033. Epub 2015 Apr 10.

Abstract

Lamellipodia, the sheet-like protrusions of motile cells, consist of networks of actin filaments (F-actin) regulated by the ordered assembly from and disassembly into actin monomers (G-actin). Traditionally, G-actin is thought to exist as a homogeneous pool. Here, we show that there are two functionally and molecularly distinct sources of G-actin that supply lamellipodial actin networks. G-actin originating from the cytosolic pool requires the monomer-binding protein thymosin β4 (Tβ4) for optimal leading-edge localization, is targeted to formins, and is responsible for creating an elevated G/F-actin ratio that promotes membrane protrusion. The second source of G-actin comes from recycled lamellipodia F-actin. Recycling occurs independently of Tβ4 and appears to regulate lamellipodia homeostasis. Tβ4-bound G-actin specifically localizes to the leading edge because it does not interact with Arp2/3-mediated polymerization sites found throughout the lamellipodia. These findings demonstrate that actin networks can be constructed from multiple sources of monomers with discrete spatiotemporal functions.

Publication types

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

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Animals
  • Cell Line
  • Cell Movement / physiology
  • Gene Knockdown Techniques
  • Image Processing, Computer-Assisted
  • Mice
  • Microscopy, Confocal
  • Pseudopodia / metabolism*