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Integration of linear and dendritic actin nucleation in Nck-induced actin comets

The Nck adaptor protein recruits cytosolic effectors such as N-WASP that induce localized actin polymerization. Experimental aggregation of Nck SH3 domains at the membrane induces actin comet tails—dynamic, elongated filamentous actin structures similar to those that drive the movement of microbial...

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Autores principales: Borinskaya, Sofya, Velle, Katrina B., Campellone, Kenneth G., Talman, Arthur, Alvarez, Diego, Agaisse, Hervé, Wu, Yi I., Loew, Leslie M., Mayer, Bruce J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713129/
https://www.ncbi.nlm.nih.gov/pubmed/26609071
http://dx.doi.org/10.1091/mbc.E14-11-1555
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author Borinskaya, Sofya
Velle, Katrina B.
Campellone, Kenneth G.
Talman, Arthur
Alvarez, Diego
Agaisse, Hervé
Wu, Yi I.
Loew, Leslie M.
Mayer, Bruce J.
author_facet Borinskaya, Sofya
Velle, Katrina B.
Campellone, Kenneth G.
Talman, Arthur
Alvarez, Diego
Agaisse, Hervé
Wu, Yi I.
Loew, Leslie M.
Mayer, Bruce J.
author_sort Borinskaya, Sofya
collection PubMed
description The Nck adaptor protein recruits cytosolic effectors such as N-WASP that induce localized actin polymerization. Experimental aggregation of Nck SH3 domains at the membrane induces actin comet tails—dynamic, elongated filamentous actin structures similar to those that drive the movement of microbial pathogens such as vaccinia virus. Here we show that experimental manipulation of the balance between unbranched/branched nucleation altered the morphology and dynamics of Nck-induced actin comets. Inhibition of linear, formin-based nucleation with the small-molecule inhibitor SMIFH2 or overexpression of the formin FH1 domain resulted in formation of predominantly circular-shaped actin structures with low mobility (actin blobs). These results indicate that formin-based linear actin polymerization is critical for the formation and maintenance of Nck-dependent actin comet tails. Consistent with this, aggregation of an exclusively branched nucleation-promoting factor (the VCA domain of N-WASP), with density and turnover similar to those of N-WASP in Nck comets, did not reconstitute dynamic, elongated actin comets. Furthermore, enhancement of branched Arp2/3-mediated nucleation by N-WASP overexpression caused loss of the typical actin comet tail shape induced by Nck aggregation. Thus the ratio of linear to dendritic nucleation activity may serve to distinguish the properties of actin structures induced by various viral and bacterial pathogens.
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spelling pubmed-47131292016-03-30 Integration of linear and dendritic actin nucleation in Nck-induced actin comets Borinskaya, Sofya Velle, Katrina B. Campellone, Kenneth G. Talman, Arthur Alvarez, Diego Agaisse, Hervé Wu, Yi I. Loew, Leslie M. Mayer, Bruce J. Mol Biol Cell Articles The Nck adaptor protein recruits cytosolic effectors such as N-WASP that induce localized actin polymerization. Experimental aggregation of Nck SH3 domains at the membrane induces actin comet tails—dynamic, elongated filamentous actin structures similar to those that drive the movement of microbial pathogens such as vaccinia virus. Here we show that experimental manipulation of the balance between unbranched/branched nucleation altered the morphology and dynamics of Nck-induced actin comets. Inhibition of linear, formin-based nucleation with the small-molecule inhibitor SMIFH2 or overexpression of the formin FH1 domain resulted in formation of predominantly circular-shaped actin structures with low mobility (actin blobs). These results indicate that formin-based linear actin polymerization is critical for the formation and maintenance of Nck-dependent actin comet tails. Consistent with this, aggregation of an exclusively branched nucleation-promoting factor (the VCA domain of N-WASP), with density and turnover similar to those of N-WASP in Nck comets, did not reconstitute dynamic, elongated actin comets. Furthermore, enhancement of branched Arp2/3-mediated nucleation by N-WASP overexpression caused loss of the typical actin comet tail shape induced by Nck aggregation. Thus the ratio of linear to dendritic nucleation activity may serve to distinguish the properties of actin structures induced by various viral and bacterial pathogens. The American Society for Cell Biology 2016-01-15 /pmc/articles/PMC4713129/ /pubmed/26609071 http://dx.doi.org/10.1091/mbc.E14-11-1555 Text en © 2016 Borinskaya et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Borinskaya, Sofya
Velle, Katrina B.
Campellone, Kenneth G.
Talman, Arthur
Alvarez, Diego
Agaisse, Hervé
Wu, Yi I.
Loew, Leslie M.
Mayer, Bruce J.
Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title_full Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title_fullStr Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title_full_unstemmed Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title_short Integration of linear and dendritic actin nucleation in Nck-induced actin comets
title_sort integration of linear and dendritic actin nucleation in nck-induced actin comets
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713129/
https://www.ncbi.nlm.nih.gov/pubmed/26609071
http://dx.doi.org/10.1091/mbc.E14-11-1555
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