Intermediate Filament Protein Partnership in Astrocytes
Open accessAbstract
Intermediate filaments are general constituents of the cytoskeleton. The function of these structures and the requirement for different types of intermediate filament proteins by individual cells are only partly understood. Here we have addressed the role of specific intermediate filament protein partnerships in the formation of intermediate filaments in astrocytes. Astrocytes may express three types of intermediate filament proteins: glial fibrillary acidic protein (GFAP), vimentin, and nestin. We used mice with targeted mutations in the GFAP or vimentin genes, or both, to study the impact of loss of either or both of these proteins on intermediate filament formation in cultured astrocytes and in normal or reactive astrocytes in vivo. We report that nestin cannot form intermediate filaments on its own, that vimentin may form intermediate filaments with either nestin or GFAP as obligatory partners, and that GFAP is the only intermediate filament protein of the three that may form filaments on its own. However, such filaments show abnormal organization. Aberrant intermediate filament formation is linked to diseases affecting epithelial, neuronal, and muscle cells. Here we present models by which the normal and pathogenic functions of intermediate filaments may be elucidated in astrocytes.
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Absence of GFAP and/or Vim in mice has no major effect under physiological conditions.
“Absence of GFAP and/or Vim in mice has no major effect under physiological conditions (17–20), reflecting the role of intermediate filament (nanofilament) system as a signaling platform in situations connected with cellular stress (21).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [20]
Gfap−/−Vim−/− astrocytes are completely devoid of intermediate filaments because nestin and synemin cannot form intermediate filaments in the absence of both GFAP and Vim.
“They are completely devoid of intermediate filaments since neither of the other two intermediate filament proteins expressed in reactive astrocytes, nestin and synemin, are able to form intermediate filaments in the absence of both GFAP and Vim (20, 22, 24).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [20]
Vim requires a second intermediate filament protein (e.g., nestin or synemin in astrocytes) to form a network.
“but Vim requires a second intermediate filament protein (e.g., nestin or synemin in astrocytes) to form a network (20, 24).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [20]
Mature astrocytes are well established to accumulate starburst bundles of GFAP filaments that fill the central cell bodies.
“As mature astrocytes are well established42 to accumulate starburst bundles of GFAP filaments that fill the central cell bodies (e.g., see Figure 3a)”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [42]
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- Authors
- Eliasson, C., Sahlgren, C., Berthold, C.-H., Stakeberg, J., Celis, J. E., Betsholtz, C., Eriksson, J. E., & Pekny, M.
- Affiliations
- University of Gothenburg (SE)
- Åbo Akademi University (FI)
- Corresponding author
- Pekny, Milos
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 274
- Issue
- 34
- Pages
- 23996-24006
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2102089332
- Cited by
- 357
- References
- 0
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 4 · 2019: 10 · 2018: 16 · 2017: 18 · 2016: 8 · 2015: 19 · 2014: 22 · 2013: 16 · 2012: 11
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TU/e Research Portal (publishedVersion)
- TU/e Research Portal (submittedVersion)
- Åbo Akademi University Research Portal (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- intermediate filaments, astrocytes, glial fibrillary acidic protein, vimentin, nestin, cytoskeleton, reactive astrocytes
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Glial Fibrillary Acidic Protein, Immunohistochemistry, Intermediate Filament Proteins, Mice, Inbred C57BL, Microscopy, Electron, Nerve Tissue Proteins, Phosphorylation, Vimentin, Mice, Nestin
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