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Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells

Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of...

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Autores principales: Ruiz-Lafuente, Natalia, Alcaraz-García, María-José, García-Serna, Azahara-María, Sebastián-Ruiz, Silvia, Moya-Quiles, María-Rosa, García-Alonso, Ana-María, Parrado, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434814/
https://www.ncbi.nlm.nih.gov/pubmed/25862245
http://dx.doi.org/10.1242/bio.20149050
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author Ruiz-Lafuente, Natalia
Alcaraz-García, María-José
García-Serna, Azahara-María
Sebastián-Ruiz, Silvia
Moya-Quiles, María-Rosa
García-Alonso, Ana-María
Parrado, Antonio
author_facet Ruiz-Lafuente, Natalia
Alcaraz-García, María-José
García-Serna, Azahara-María
Sebastián-Ruiz, Silvia
Moya-Quiles, María-Rosa
García-Alonso, Ana-María
Parrado, Antonio
author_sort Ruiz-Lafuente, Natalia
collection PubMed
description Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells.
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spelling pubmed-44348142015-06-11 Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells Ruiz-Lafuente, Natalia Alcaraz-García, María-José García-Serna, Azahara-María Sebastián-Ruiz, Silvia Moya-Quiles, María-Rosa García-Alonso, Ana-María Parrado, Antonio Biol Open Research Article Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells. The Company of Biologists 2015-04-10 /pmc/articles/PMC4434814/ /pubmed/25862245 http://dx.doi.org/10.1242/bio.20149050 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Ruiz-Lafuente, Natalia
Alcaraz-García, María-José
García-Serna, Azahara-María
Sebastián-Ruiz, Silvia
Moya-Quiles, María-Rosa
García-Alonso, Ana-María
Parrado, Antonio
Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title_full Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title_fullStr Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title_full_unstemmed Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title_short Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells
title_sort dock10, a cdc42 and rac1 gef, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial hela cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434814/
https://www.ncbi.nlm.nih.gov/pubmed/25862245
http://dx.doi.org/10.1242/bio.20149050
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