- Title
- Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes
- Creator
- de Pablo, Yolanda; Marasek, Pavel; Pozo-Rodrigalvarez, Andrea; Wilhelmsson, Ulrika; Inagaki, Masaki; Pekna, Marcela; Pekny, Milos
- Relation
- Cells Vol. 8, Issue 9
- Publisher Link
- http://dx.doi.org/10.3390/cells8091016
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- intermediate filaments; nanofilaments; vimentin; vimentin accumulations; GFAP; astrocytes; immature astrocytes; mitochondria
- Identifier
- http://hdl.handle.net/1959.13/1456613
- Identifier
- uon:45247
- Identifier
- ISSN:2073-4409
- Rights
- This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
- Language
- eng
- Full Text
- Reviewed
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