Profilin2 regulates actin rod assembly in neuronal cells

Abstract Nuclear and cytoplasmic actin-cofilin rods are formed transiently under stress conditions to reduce actin filament turnover and ATP hydrolysis. The persistence of these structures has been implicated in disease pathology of several neurological disorders. Recently, the presence of actin rod...

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Autores principales:	Lisa Marie Walter, Sebastian Rademacher, Andreas Pich, Peter Claus
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8675360be3134e99aa21bbd472c74877
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spelling	oai:doaj.org-article:8675360be3134e99aa21bbd472c748772021-12-02T17:15:22ZProfilin2 regulates actin rod assembly in neuronal cells10.1038/s41598-021-89397-92045-2322https://doaj.org/article/8675360be3134e99aa21bbd472c748772021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89397-9https://doaj.org/toc/2045-2322Abstract Nuclear and cytoplasmic actin-cofilin rods are formed transiently under stress conditions to reduce actin filament turnover and ATP hydrolysis. The persistence of these structures has been implicated in disease pathology of several neurological disorders. Recently, the presence of actin rods has been discovered in Spinal Muscular Atrophy (SMA), a neurodegenerative disease affecting predominantly motoneurons leading to muscle weakness and atrophy. This finding underlined the importance of dysregulated actin dynamics in motoneuron loss in SMA. In this study, we characterized actin rods formed in a SMA cell culture model analyzing their composition by LC–MS-based proteomics. Besides actin and cofilin, we identified proteins involved in processes such as ubiquitination, translation or protein folding to be bound to actin rods. This suggests their sequestration to actin rods, thus impairing important cellular functions. Moreover, we showed the involvement of the cytoskeletal protein profilin2 and its upstream effectors RhoA/ROCK in actin rod assembly in SMA. These findings implicate that the formation of actin rods exerts detrimental effects on motoneuron homeostasis by affecting actin dynamics and disturbing essential cellular pathways.Lisa Marie WalterSebastian RademacherAndreas PichPeter ClausNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lisa Marie Walter Sebastian Rademacher Andreas Pich Peter Claus Profilin2 regulates actin rod assembly in neuronal cells
description	Abstract Nuclear and cytoplasmic actin-cofilin rods are formed transiently under stress conditions to reduce actin filament turnover and ATP hydrolysis. The persistence of these structures has been implicated in disease pathology of several neurological disorders. Recently, the presence of actin rods has been discovered in Spinal Muscular Atrophy (SMA), a neurodegenerative disease affecting predominantly motoneurons leading to muscle weakness and atrophy. This finding underlined the importance of dysregulated actin dynamics in motoneuron loss in SMA. In this study, we characterized actin rods formed in a SMA cell culture model analyzing their composition by LC–MS-based proteomics. Besides actin and cofilin, we identified proteins involved in processes such as ubiquitination, translation or protein folding to be bound to actin rods. This suggests their sequestration to actin rods, thus impairing important cellular functions. Moreover, we showed the involvement of the cytoskeletal protein profilin2 and its upstream effectors RhoA/ROCK in actin rod assembly in SMA. These findings implicate that the formation of actin rods exerts detrimental effects on motoneuron homeostasis by affecting actin dynamics and disturbing essential cellular pathways.
format	article
author	Lisa Marie Walter Sebastian Rademacher Andreas Pich Peter Claus
author_facet	Lisa Marie Walter Sebastian Rademacher Andreas Pich Peter Claus
author_sort	Lisa Marie Walter
title	Profilin2 regulates actin rod assembly in neuronal cells
title_short	Profilin2 regulates actin rod assembly in neuronal cells
title_full	Profilin2 regulates actin rod assembly in neuronal cells
title_fullStr	Profilin2 regulates actin rod assembly in neuronal cells
title_full_unstemmed	Profilin2 regulates actin rod assembly in neuronal cells
title_sort	profilin2 regulates actin rod assembly in neuronal cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8675360be3134e99aa21bbd472c74877
work_keys_str_mv	AT lisamariewalter profilin2regulatesactinrodassemblyinneuronalcells AT sebastianrademacher profilin2regulatesactinrodassemblyinneuronalcells AT andreaspich profilin2regulatesactinrodassemblyinneuronalcells AT peterclaus profilin2regulatesactinrodassemblyinneuronalcells
_version_	1718381268869054464

Profilin2 regulates actin rod assembly in neuronal cells

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