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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2021-05-01
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Online Access: | https://doi.org/10.1038/s41598-021-89397-9 |
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doaj-8675360be3134e99aa21bbd472c748772021-05-16T11:26:52ZengNature Publishing GroupScientific Reports2045-23222021-05-0111111310.1038/s41598-021-89397-9Profilin2 regulates actin rod assembly in neuronal cellsLisa Marie Walter0Sebastian Rademacher1Andreas Pich2Peter Claus3Institute of Neuroanatomy and Cell Biology, Hannover Medical SchoolInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolInstitute of Toxicology and Core Unit Proteomics, Hannover Medical SchoolInstitute of Neuroanatomy and Cell Biology, Hannover Medical SchoolAbstract 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.https://doi.org/10.1038/s41598-021-89397-9 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisa Marie Walter Sebastian Rademacher Andreas Pich Peter Claus |
spellingShingle |
Lisa Marie Walter Sebastian Rademacher Andreas Pich Peter Claus Profilin2 regulates actin rod assembly in neuronal cells Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-05-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-89397-9 |
work_keys_str_mv |
AT lisamariewalter profilin2regulatesactinrodassemblyinneuronalcells AT sebastianrademacher profilin2regulatesactinrodassemblyinneuronalcells AT andreaspich profilin2regulatesactinrodassemblyinneuronalcells AT peterclaus profilin2regulatesactinrodassemblyinneuronalcells |
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