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

doi:10.1016/j.cub.2013.04.057

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^*

^*Corresponding author for this work

Department of Biology

Research output: Contribution to journal › Journal article › peer-review

73 Citations (Scopus)

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 language	English
Pages (from-to)	1046-1056
Number of pages	11
Journal	Current Biology
Volume	23
Issue number	12
DOIs	https://doi.org/10.1016/j.cub.2013.04.057
Publication status	Published - 17 Jun 2013

Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cub.2013.04.057

Cite this

@article{795b2b5ef5794b669333c7cb7f0be662,

title = "Dynamic localization of G-actin during membrane protrusion in neuronal motility",

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.",

author = "Lee, {Chi Wai} and Vitriol, {Eric A.} and Sangwoo Shim and Wise, {Ariel L.} and Velayutham, {Radhi P.} and Zheng, {James Q.}",

note = "Funding Information: We would like to thank James R. Bamburg (Colorado State University–Fort Collins) for input and discussion on the manuscript and William Bement (University of Wisconsin–Madison) for the suggestion of the experiments involving actin drugs. We are grateful to Nikon Instruments for providing an N-SIM system for our superresolution imaging. This project is supported in part by research grants from National Institutes of Health to J.Q.Z., a research development grant from the Muscular Dystrophy Association to C.W.L., a F32 fellowship award from National Institutes of Health to E.A.V., and a National Institute of Neurological Disorders and Stroke core facilities grant (P30NS055077) to the Integrated Cellular Imaging Microscopy Core of Emory Neuroscience. Publisher copyright: {\textcopyright} 2013 Elsevier Ltd. All rights reserved. ",

year = "2013",

month = jun,

day = "17",

doi = "10.1016/j.cub.2013.04.057",

language = "English",

volume = "23",

pages = "1046--1056",

journal = "Current Biology",

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T1 - Dynamic localization of G-actin during membrane protrusion in neuronal motility

AU - Lee, Chi Wai

AU - Vitriol, Eric A.

AU - Shim, Sangwoo

AU - Wise, Ariel L.

AU - Velayutham, Radhi P.

AU - Zheng, James Q.

N1 - Funding Information: We would like to thank James R. Bamburg (Colorado State University–Fort Collins) for input and discussion on the manuscript and William Bement (University of Wisconsin–Madison) for the suggestion of the experiments involving actin drugs. We are grateful to Nikon Instruments for providing an N-SIM system for our superresolution imaging. This project is supported in part by research grants from National Institutes of Health to J.Q.Z., a research development grant from the Muscular Dystrophy Association to C.W.L., a F32 fellowship award from National Institutes of Health to E.A.V., and a National Institute of Neurological Disorders and Stroke core facilities grant (P30NS055077) to the Integrated Cellular Imaging Microscopy Core of Emory Neuroscience. Publisher copyright: © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/6/17

Y1 - 2013/6/17

N2 - 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.

AB - 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.

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DO - 10.1016/j.cub.2013.04.057

M3 - Journal article

C2 - 23746641

AN - SCOPUS:84879286502

SN - 0960-9822

VL - 23

SP - 1046

EP - 1056

JO - Current Biology

JF - Current Biology

IS - 12

ER -

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

Abstract

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