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Open AccessArticle

Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes

1
Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 40530 Gothenburg, Sweden
2
Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 40530 Gothenburg, Sweden
3
Department of Physiology, Mie University Graduate School of Medicine, Mie 5148507, Japan
4
Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia
5
University of Newcastle, New South Wales 2308, Australia
*
Author to whom correspondence should be addressed.
Cells 2019, 8(9), 1016; https://doi.org/10.3390/cells8091016
Received: 29 July 2019 / Revised: 20 August 2019 / Accepted: 28 August 2019 / Published: 1 September 2019
(This article belongs to the Special Issue Astrocytes in Space and Time)
Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP−/− mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP−/− background. This indicates that the disappearance of vimentin accumulations and cytokinetic failure in mature astrocyte cultures are independent of GFAP expression. Both VIMSA/SA and VIMSA/SAGFAP−/− astrocytes showed normal mitochondrial membrane potential and vulnerability to H2O2, oxygen/glucose deprivation, and chemical ischemia. Thus, mutation of mitotic phosphorylation sites in vimentin triggers formation of vimentin accumulations and cytokinetic failure in immature astrocytes without altering their vulnerability to oxidative stress. View Full-Text
Keywords: intermediate filaments; nanofilaments; vimentin; vimentin accumulations; GFAP; astrocytes; immature astrocytes; mitochondria intermediate filaments; nanofilaments; vimentin; vimentin accumulations; GFAP; astrocytes; immature astrocytes; mitochondria
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MDPI and ACS Style

Pablo, Y.d.; Marasek, P.; Pozo-Rodrigálvarez, A.; Wilhelmsson, U.; Inagaki, M.; Pekna, M.; Pekny, M. Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes. Cells 2019, 8, 1016. https://doi.org/10.3390/cells8091016

AMA Style

Pablo Yd, Marasek P, Pozo-Rodrigálvarez A, Wilhelmsson U, Inagaki M, Pekna M, Pekny M. Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes. Cells. 2019; 8(9):1016. https://doi.org/10.3390/cells8091016

Chicago/Turabian Style

Pablo, Yolanda de; Marasek, Pavel; Pozo-Rodrigálvarez, Andrea; Wilhelmsson, Ulrika; Inagaki, Masaki; Pekna, Marcela; Pekny, Milos. 2019. "Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes" Cells 8, no. 9: 1016. https://doi.org/10.3390/cells8091016

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