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Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability
Von Hippel-Lindau (VHL) tumor suppressor gene mutations predispose carriers to kidney cancer. The protein pVHL has been shown to interact with microtubules (MTs), which is critical to cilia maintenance and mitotic spindle orientation. However, the function for pVHL in the regulation of MT dynamics i...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101603/ https://www.ncbi.nlm.nih.gov/pubmed/20855504 http://dx.doi.org/10.1083/jcb.201006059 |
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author | Thoma, Claudio R. Matov, Alexandre Gutbrodt, Katrin L. Hoerner, Christian R. Smole, Zlatko Krek, Wilhelm Danuser, Gaudenz |
author_facet | Thoma, Claudio R. Matov, Alexandre Gutbrodt, Katrin L. Hoerner, Christian R. Smole, Zlatko Krek, Wilhelm Danuser, Gaudenz |
author_sort | Thoma, Claudio R. |
collection | PubMed |
description | Von Hippel-Lindau (VHL) tumor suppressor gene mutations predispose carriers to kidney cancer. The protein pVHL has been shown to interact with microtubules (MTs), which is critical to cilia maintenance and mitotic spindle orientation. However, the function for pVHL in the regulation of MT dynamics is unknown. We tracked MT growth via the plus end marker EB3 (end-binding protein 3)-GFP and inferred additional parameters of MT dynamics indirectly by spatiotemporal grouping of growth tracks from live cell imaging. Our data establish pVHL as a near-optimal MT-stabilizing protein: it attenuates tubulin turnover, both during MT growth and shrinkage, inhibits catastrophe, and enhances rescue frequencies. These functions are mediated, in part, by inhibition of tubulin guanosine triphosphatase activity in vitro and at MT plus ends and along the MT lattice in vivo. Mutants connected to the VHL cancer syndrome are differentially compromised in these activities. Thus, single cell–level analysis of pVHL MT regulatory function allows new predictions for genotype to phenotype associations that deviate from the coarser clinically defined mutant classifications. |
format | Text |
id | pubmed-3101603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31016032011-06-06 Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability Thoma, Claudio R. Matov, Alexandre Gutbrodt, Katrin L. Hoerner, Christian R. Smole, Zlatko Krek, Wilhelm Danuser, Gaudenz J Cell Biol Research Articles Von Hippel-Lindau (VHL) tumor suppressor gene mutations predispose carriers to kidney cancer. The protein pVHL has been shown to interact with microtubules (MTs), which is critical to cilia maintenance and mitotic spindle orientation. However, the function for pVHL in the regulation of MT dynamics is unknown. We tracked MT growth via the plus end marker EB3 (end-binding protein 3)-GFP and inferred additional parameters of MT dynamics indirectly by spatiotemporal grouping of growth tracks from live cell imaging. Our data establish pVHL as a near-optimal MT-stabilizing protein: it attenuates tubulin turnover, both during MT growth and shrinkage, inhibits catastrophe, and enhances rescue frequencies. These functions are mediated, in part, by inhibition of tubulin guanosine triphosphatase activity in vitro and at MT plus ends and along the MT lattice in vivo. Mutants connected to the VHL cancer syndrome are differentially compromised in these activities. Thus, single cell–level analysis of pVHL MT regulatory function allows new predictions for genotype to phenotype associations that deviate from the coarser clinically defined mutant classifications. The Rockefeller University Press 2010-09-20 /pmc/articles/PMC3101603/ /pubmed/20855504 http://dx.doi.org/10.1083/jcb.201006059 Text en © 2010 Thoma et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Thoma, Claudio R. Matov, Alexandre Gutbrodt, Katrin L. Hoerner, Christian R. Smole, Zlatko Krek, Wilhelm Danuser, Gaudenz Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title | Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title_full | Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title_fullStr | Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title_full_unstemmed | Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title_short | Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability |
title_sort | quantitative image analysis identifies pvhl as a key regulator of microtubule dynamic instability |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101603/ https://www.ncbi.nlm.nih.gov/pubmed/20855504 http://dx.doi.org/10.1083/jcb.201006059 |
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