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The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling

L-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependen...

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Autores principales: Ishida, Hiroaki, Jensen, Katharine V., Woodman, Andrew G., Hyndman, M. Eric, Vogel, Hans J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286426/
https://www.ncbi.nlm.nih.gov/pubmed/28145401
http://dx.doi.org/10.1038/srep40662
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author Ishida, Hiroaki
Jensen, Katharine V.
Woodman, Andrew G.
Hyndman, M. Eric
Vogel, Hans J.
author_facet Ishida, Hiroaki
Jensen, Katharine V.
Woodman, Andrew G.
Hyndman, M. Eric
Vogel, Hans J.
author_sort Ishida, Hiroaki
collection PubMed
description L-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependent regulation of the actin-bundling activity of L-plastin is not well understood. We have used NMR spectroscopy to determine the solution structure of the EF-hand calcium-sensor headpiece domain. Unexpectedly, this domain does not bind directly to the four CH-domains of L-plastin. A novel switch helix is present immediately after the calcium-binding region and it binds tightly to the EF-hand motifs in the presence of calcium. We demonstrate that this switch helix plays a major role during actin-bundling. Moreover a peptide that competitively inhibits the association between the EF-hand motifs and the switch helix was shown to deregulate the actin-bundling activity of L-plastin. Overall, these findings may help to develop new drugs that target the L-plastin headpiece and interfere in the metastatic activity of cancer cells.
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spelling pubmed-52864262017-02-06 The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling Ishida, Hiroaki Jensen, Katharine V. Woodman, Andrew G. Hyndman, M. Eric Vogel, Hans J. Sci Rep Article L-plastin is a calcium-regulated actin-bundling protein that is expressed in cells of hematopoietic origin and in most metastatic cancer cells. These cell types are mobile and require the constant remodeling of their actin cytoskeleton, where L-plastin bundles filamentous actin. The calcium-dependent regulation of the actin-bundling activity of L-plastin is not well understood. We have used NMR spectroscopy to determine the solution structure of the EF-hand calcium-sensor headpiece domain. Unexpectedly, this domain does not bind directly to the four CH-domains of L-plastin. A novel switch helix is present immediately after the calcium-binding region and it binds tightly to the EF-hand motifs in the presence of calcium. We demonstrate that this switch helix plays a major role during actin-bundling. Moreover a peptide that competitively inhibits the association between the EF-hand motifs and the switch helix was shown to deregulate the actin-bundling activity of L-plastin. Overall, these findings may help to develop new drugs that target the L-plastin headpiece and interfere in the metastatic activity of cancer cells. Nature Publishing Group 2017-02-01 /pmc/articles/PMC5286426/ /pubmed/28145401 http://dx.doi.org/10.1038/srep40662 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ishida, Hiroaki
Jensen, Katharine V.
Woodman, Andrew G.
Hyndman, M. Eric
Vogel, Hans J.
The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title_full The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title_fullStr The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title_full_unstemmed The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title_short The Calcium-Dependent Switch Helix of L-Plastin Regulates Actin Bundling
title_sort calcium-dependent switch helix of l-plastin regulates actin bundling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286426/
https://www.ncbi.nlm.nih.gov/pubmed/28145401
http://dx.doi.org/10.1038/srep40662
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