Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins
Cytoplasmic intermediate filaments (IFs) surround the nucleus and are often anchored at membrane sites to form effectively transcellular networks. Mutations in IF proteins (IFps) have revealed mechanical roles in epidermis, muscle, liver, and neurons. At the same time, there have been phenotypic sur...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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F1000 Research Limited
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774051/ https://www.ncbi.nlm.nih.gov/pubmed/31602295 http://dx.doi.org/10.12688/f1000research.19950.1 |
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author | Klymkowsky, Michael W. |
author_facet | Klymkowsky, Michael W. |
author_sort | Klymkowsky, Michael W. |
collection | PubMed |
description | Cytoplasmic intermediate filaments (IFs) surround the nucleus and are often anchored at membrane sites to form effectively transcellular networks. Mutations in IF proteins (IFps) have revealed mechanical roles in epidermis, muscle, liver, and neurons. At the same time, there have been phenotypic surprises, illustrated by the ability to generate viable and fertile mice null for a number of IFp-encoding genes, including vimentin. Yet in humans, the vimentin ( VIM) gene displays a high probability of intolerance to loss-of-function mutations, indicating an essential role. A number of subtle and not so subtle IF-associated phenotypes have been identified, often linked to mechanical or metabolic stresses, some of which have been found to be ameliorated by the over-expression of molecular chaperones, suggesting that such phenotypes arise from what might be termed “orphan” effects as opposed to the absence of the IF network per se, an idea originally suggested by Toivola et al. and Pekny and Lane. |
format | Online Article Text |
id | pubmed-6774051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | F1000 Research Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-67740512019-10-09 Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins Klymkowsky, Michael W. F1000Res Review Cytoplasmic intermediate filaments (IFs) surround the nucleus and are often anchored at membrane sites to form effectively transcellular networks. Mutations in IF proteins (IFps) have revealed mechanical roles in epidermis, muscle, liver, and neurons. At the same time, there have been phenotypic surprises, illustrated by the ability to generate viable and fertile mice null for a number of IFp-encoding genes, including vimentin. Yet in humans, the vimentin ( VIM) gene displays a high probability of intolerance to loss-of-function mutations, indicating an essential role. A number of subtle and not so subtle IF-associated phenotypes have been identified, often linked to mechanical or metabolic stresses, some of which have been found to be ameliorated by the over-expression of molecular chaperones, suggesting that such phenotypes arise from what might be termed “orphan” effects as opposed to the absence of the IF network per se, an idea originally suggested by Toivola et al. and Pekny and Lane. F1000 Research Limited 2019-09-30 /pmc/articles/PMC6774051/ /pubmed/31602295 http://dx.doi.org/10.12688/f1000research.19950.1 Text en Copyright: © 2019 Klymkowsky MW http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Klymkowsky, Michael W. Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title | Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title_full | Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title_fullStr | Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title_full_unstemmed | Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title_short | Filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
title_sort | filaments and phenotypes: cellular roles and orphan effects associated with mutations in cytoplasmic intermediate filament proteins |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774051/ https://www.ncbi.nlm.nih.gov/pubmed/31602295 http://dx.doi.org/10.12688/f1000research.19950.1 |
work_keys_str_mv | AT klymkowskymichaelw filamentsandphenotypescellularrolesandorphaneffectsassociatedwithmutationsincytoplasmicintermediatefilamentproteins |