Dynamic Localization of G-Actin during Membrane Protrusion in Neuronal Motility

• Type of Material: Article
• Authors: Chi Wai Lee, Emory University; Eric A. Vitriol, Emory University; Sangwoo Shim, Emory University; Ariel L. Wise, Emory University; Radhi P. Velayutham, Emory University; James Zheng, Emory University
• Language: English
• Date: 2013-06-17
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cub.2013.04.057
• Title of Journal or Parent Work: Current Biology
• ISSN: 0960-9822
• Volume: 23
• Issue: 12
• Start Page: 1046
• End Page: 1056
• Grant/Funding Information: This project is supported in part by research grants from National Institutes of Health to JQZ, a research development grant from Muscular Dystrophy Association to CWL, a F32 fellowship award from National Institutes of Health to EAV, and an NINDS core facilities grant (P30NS055077) to the Integrated Cellular Imaging Microscopy Core of Emory Neuroscience.
• Keywords: PROTEINS; BINDING; Life Sciences & Biomedicine; F-ACTIN; CYTOSKELETAL DYNAMICS; AXON GUIDANCE; VERTEBRATE GASTRULATION; MOLECULAR-MECHANISMS; CULTURED-CELLS; Science & Technology; Biochemistry & Molecular Biology; POLYMERIZATION; GROWTH CONES; Cell Biology
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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.