Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells

Abstract Intermediate filament polypeptides (IFPs) are prominent components of cytoplasmic aggregates, which are pathognomonic for multiple diseases. Recent observations in cultured cells suggest that they are dynamic and subject to regulated turnover. The emerging concept is that multiple factors c...

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Autores principales:	S. M. Lehmann, R. E. Leube, R. Windoffer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/460cb2d6716842a2811baa6bfd63d084
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spelling	oai:doaj.org-article:460cb2d6716842a2811baa6bfd63d0842021-12-02T14:16:17ZGrowth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells10.1038/s41598-021-81542-82045-2322https://doaj.org/article/460cb2d6716842a2811baa6bfd63d0842021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81542-8https://doaj.org/toc/2045-2322Abstract Intermediate filament polypeptides (IFPs) are prominent components of cytoplasmic aggregates, which are pathognomonic for multiple diseases. Recent observations in cultured cells suggest that they are dynamic and subject to regulated turnover. The emerging concept is that multiple factors contribute to motility and turnover of IFP-containing aggregates. To understand their relative contribution, quantitative tools are needed. The current study addresses this need using epithelial cells producing mutant keratin IFPs that have been identified as the cause of the hereditary blister-forming skin disease epidermolysis bullosa simplex. Digital image analysis of individual granules allowed mapping of their complete life cycle, with information on multiple characteristics at any given time-point. The deduced signet features revealed rapid granule fusion and directed transport from the periphery towards the cell centre, and a limited, ~ 30 min lifetime with a slow, continuous growth phase followed by fast disassembly. As paradigmatic proof-of-principle, we demonstrate that inhibition of myosin II selectively reduces granule movement, linking keratin granule motility to retrograde cortical acto-myosin flow. The newly developed methods and established parameters will help in the characterization of known and the identification of novel regulators of IFP-containing aggregates.S. M. LehmannR. E. LeubeR. WindofferNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. M. Lehmann R. E. Leube R. Windoffer Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
description	Abstract Intermediate filament polypeptides (IFPs) are prominent components of cytoplasmic aggregates, which are pathognomonic for multiple diseases. Recent observations in cultured cells suggest that they are dynamic and subject to regulated turnover. The emerging concept is that multiple factors contribute to motility and turnover of IFP-containing aggregates. To understand their relative contribution, quantitative tools are needed. The current study addresses this need using epithelial cells producing mutant keratin IFPs that have been identified as the cause of the hereditary blister-forming skin disease epidermolysis bullosa simplex. Digital image analysis of individual granules allowed mapping of their complete life cycle, with information on multiple characteristics at any given time-point. The deduced signet features revealed rapid granule fusion and directed transport from the periphery towards the cell centre, and a limited, ~ 30 min lifetime with a slow, continuous growth phase followed by fast disassembly. As paradigmatic proof-of-principle, we demonstrate that inhibition of myosin II selectively reduces granule movement, linking keratin granule motility to retrograde cortical acto-myosin flow. The newly developed methods and established parameters will help in the characterization of known and the identification of novel regulators of IFP-containing aggregates.
format	article
author	S. M. Lehmann R. E. Leube R. Windoffer
author_facet	S. M. Lehmann R. E. Leube R. Windoffer
author_sort	S. M. Lehmann
title	Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
title_short	Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
title_full	Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
title_fullStr	Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
title_full_unstemmed	Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
title_sort	growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/460cb2d6716842a2811baa6bfd63d084
work_keys_str_mv	AT smlehmann growthlifetimedirectionalmovementandmyosindependentmotilityofmutantkeratingranulesinculturedcells AT releube growthlifetimedirectionalmovementandmyosindependentmotilityofmutantkeratingranulesinculturedcells AT rwindoffer growthlifetimedirectionalmovementandmyosindependentmotilityofmutantkeratingranulesinculturedcells
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Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells

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