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

Two functionally distinct sources of actin monomers supply the leading edge of lamellipodia.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: evitriol@ufl.edu.
2
Department of Physics, Lehigh University, Bethlehem, PA 18015, USA.
3
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
4
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.
5
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.

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.

PMID:
25865895
PMCID:
PMC4418508
DOI:
10.1016/j.celrep.2015.03.033
[Indexed for MEDLINE]
Free PMC Article

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