Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1

Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance si...

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Main Authors: Lebrand, Cecile, Lanier, Lorene M., Krause, Matthias, Svitkina, Tatyana M., Borisy, Gary G., Dent, Erik W., Strasser, Geraldine A., Gertler, Frank
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2014
Online Access:http://hdl.handle.net/1721.1/83481
https://orcid.org/0000-0001-8525-7136
https://orcid.org/0000-0003-3214-4554
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author Lebrand, Cecile
Lanier, Lorene M.
Krause, Matthias
Svitkina, Tatyana M.
Borisy, Gary G.
Dent, Erik W.
Strasser, Geraldine A.
Gertler, Frank
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Lebrand, Cecile
Lanier, Lorene M.
Krause, Matthias
Svitkina, Tatyana M.
Borisy, Gary G.
Dent, Erik W.
Strasser, Geraldine A.
Gertler, Frank
author_sort Lebrand, Cecile
collection MIT
description Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and elongation of filopodia along neurite shafts and growth cone. Netrin-1-induced filopodia formation was dependent upon Ena/VASP function and directly correlated with Ena/VASP phosphorylation at a regulatory PKA site. Accordingly, Ena/VASP function was required for filopodial formation from the growth cone in response to global PKA activation. We propose that Ena/VASP proteins control filopodial dynamics in neurons by remodeling the actin network in response to guidance cues.
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spelling mit-1721.1/834812022-09-28T14:25:27Z Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1 Lebrand, Cecile Lanier, Lorene M. Krause, Matthias Svitkina, Tatyana M. Borisy, Gary G. Dent, Erik W. Strasser, Geraldine A. Gertler, Frank Massachusetts Institute of Technology. Department of Biology Dent, Erik W. Strasser, Geraldine A. Krause, Matthias Gertler, Frank Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and elongation of filopodia along neurite shafts and growth cone. Netrin-1-induced filopodia formation was dependent upon Ena/VASP function and directly correlated with Ena/VASP phosphorylation at a regulatory PKA site. Accordingly, Ena/VASP function was required for filopodial formation from the growth cone in response to global PKA activation. We propose that Ena/VASP proteins control filopodial dynamics in neurons by remodeling the actin network in response to guidance cues. W. M. Keck Foundation (Distinguished Young Scholar Award) National Institutes of Health (U.S.) (Grant NS45366) Cell Migration Consortium (Grant GM68678) 2014-01-06T15:44:27Z 2014-01-06T15:44:27Z 2004-04 2003-12 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/83481 Lebrand, Cecile, Erik W Dent, Geraldine A Strasser, Lorene M Lanier, Matthias Krause, Tatyana M Svitkina, Gary G Borisy, and Frank B Gertler. “Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1.” Neuron 42, no. 1 (April 2004): 37-49. Copyright © 2004 Cell Press https://orcid.org/0000-0001-8525-7136 https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1016/S0896-6273(04)00108-4 Neuron Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive
spellingShingle Lebrand, Cecile
Lanier, Lorene M.
Krause, Matthias
Svitkina, Tatyana M.
Borisy, Gary G.
Dent, Erik W.
Strasser, Geraldine A.
Gertler, Frank
Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title_full Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title_fullStr Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title_full_unstemmed Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title_short Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of Netrin-1
title_sort critical role of ena vasp proteins for filopodia formation in neurons and in function downstream of netrin 1
url http://hdl.handle.net/1721.1/83481
https://orcid.org/0000-0001-8525-7136
https://orcid.org/0000-0003-3214-4554
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