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Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration

BACKGROUND: Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise function of PC-1 remains elusive, although several studies s...

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Autores principales: Castelli, Maddalena, De Pascalis, Chiara, Distefano, Gianfranco, Ducano, Nadia, Oldani, Amanda, Lanzetti, Letizia, Boletta, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437554/
https://www.ncbi.nlm.nih.gov/pubmed/25947155
http://dx.doi.org/10.1186/s12860-015-0059-3
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author Castelli, Maddalena
De Pascalis, Chiara
Distefano, Gianfranco
Ducano, Nadia
Oldani, Amanda
Lanzetti, Letizia
Boletta, Alessandra
author_facet Castelli, Maddalena
De Pascalis, Chiara
Distefano, Gianfranco
Ducano, Nadia
Oldani, Amanda
Lanzetti, Letizia
Boletta, Alessandra
author_sort Castelli, Maddalena
collection PubMed
description BACKGROUND: Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise function of PC-1 remains elusive, although several studies suggest that it can regulate the cellular shape in response to external stimuli. We and others reported that PC-1 regulates the actin cytoskeleton and cell migration. RESULTS: Here we show that cells over-expressing PC-1 display enhanced adhesion rates to the substrate, while cells lacking PC-1 have a reduced capability to adhere. In search for the mechanism responsible for this new property of PC-1 we found that this receptor is able to regulate the stability of the microtubules, in addition to its capability to regulate the actin cytoskeleton. The two cytoskeletal components are acting in a coordinated fashion. Notably, we uncovered that PC-1 regulation of the microtubule cytoskeleton impacts on the turnover rates of focal adhesions in migrating cells and we link all these properties to the capability of PC-1 to regulate the activation state of Focal Adhesion Kinase (FAK). CONCLUSIONS: In this study we show several new features of the PC-1 receptor in modulating microtubules and adhesion dynamics, which are essential for its capability to regulate migration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-015-0059-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-44375542015-05-20 Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration Castelli, Maddalena De Pascalis, Chiara Distefano, Gianfranco Ducano, Nadia Oldani, Amanda Lanzetti, Letizia Boletta, Alessandra BMC Cell Biol Research Article BACKGROUND: Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise function of PC-1 remains elusive, although several studies suggest that it can regulate the cellular shape in response to external stimuli. We and others reported that PC-1 regulates the actin cytoskeleton and cell migration. RESULTS: Here we show that cells over-expressing PC-1 display enhanced adhesion rates to the substrate, while cells lacking PC-1 have a reduced capability to adhere. In search for the mechanism responsible for this new property of PC-1 we found that this receptor is able to regulate the stability of the microtubules, in addition to its capability to regulate the actin cytoskeleton. The two cytoskeletal components are acting in a coordinated fashion. Notably, we uncovered that PC-1 regulation of the microtubule cytoskeleton impacts on the turnover rates of focal adhesions in migrating cells and we link all these properties to the capability of PC-1 to regulate the activation state of Focal Adhesion Kinase (FAK). CONCLUSIONS: In this study we show several new features of the PC-1 receptor in modulating microtubules and adhesion dynamics, which are essential for its capability to regulate migration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-015-0059-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-07 /pmc/articles/PMC4437554/ /pubmed/25947155 http://dx.doi.org/10.1186/s12860-015-0059-3 Text en © Castelli et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Castelli, Maddalena
De Pascalis, Chiara
Distefano, Gianfranco
Ducano, Nadia
Oldani, Amanda
Lanzetti, Letizia
Boletta, Alessandra
Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title_full Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title_fullStr Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title_full_unstemmed Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title_short Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
title_sort regulation of the microtubular cytoskeleton by polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437554/
https://www.ncbi.nlm.nih.gov/pubmed/25947155
http://dx.doi.org/10.1186/s12860-015-0059-3
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