Dynamic localization of G-actin during membrane protrusion in neuronal motility

Chi Wai Lee, Eric A. Vitriol, Sangwoo Shim, Ariel L. Wise, Radhi P. Velayutham, James Q. Zheng

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Background Actin-based cell motility is fundamental for development, function, and malignant events in eukaryotic organisms. During neural development, axonal growth cones depend on rapid assembly and disassembly of actin filaments (F-actin) for their guided extension to specific targets for wiring. Monomeric globular actin (G-actin) is the building block for F-actin but is not considered to play a direct role in spatiotemporal control of actin dynamics in cell motility. Results Here we report that a pool of G-actin dynamically localizes to the leading edge of growth cones and neuroblastoma cells to spatially elevate the G-/F-actin ratio that drives membrane protrusion and cell movement. Loss of G-actin localization leads to the cessation and retraction of membrane protrusions. Moreover, G-actin localization occurs asymmetrically in growth cones during attractive turning. Finally, we identify the actin monomer-binding proteins profilin and thymosin β4 as key molecules that localize actin monomers to the leading edge of lamellipodia for their motility. Conclusions Our results suggest that dynamic localization of G-actin provides a novel mechanism to regulate the spatiotemporal actin dynamics underlying membrane protrusion in cell locomotion and growth cone chemotaxis.

Original languageEnglish (US)
Pages (from-to)1046-1056
Number of pages11
JournalCurrent Biology
Volume23
Issue number12
DOIs
StatePublished - Jun 17 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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