title: Two functionally distinct sources of actin monomers supply the leading edge of lamellipodia.
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.
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: evitriol@ufl.edu.
authors: Eric A
authors: EA
authors: Vitriol
authors: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
authors: Laura M
authors: LM
authors: McMillen
authors: Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Maryna
authors: M
authors: Kapustina
authors: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Shawn M
authors: SM
authors: Gomez
authors: Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
authors: Dimitrios
authors: D
authors: Vavylonis
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: james.zheng@emory.edu.
authors: James Q
authors: JQ
authors: Zheng
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D055785:Gene Knockdown Techniques; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018613:Microscopy, Confocal; D011554:Pseudopodia / Q000378:metabolism*