Intermediate Filament Protein Partnership in Astrocytes*
- Camilla Eliasson‡,
- Cecilia Sahlgren§,
- Claes-Henric Berthold¶,
- Josefina Stakeberg‡,
- Julio E. Celis‖,
- Christer Betsholtz‡,
- John E. Eriksson** and
- Milos Pekny‡‡
- From the ‡Department of Medical Biochemistry, University of Gothenburg, SE-405 30 Gothenburg, Sweden, the§Department of Biology, Åbo Akademi University, Turku 20520, Finland, the ¶Department of Anatomy and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden, the‖Danish Center for Human Genome Research, Aarhus 8000, Denmark, and the **Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku 20520, Finland
Abstract
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 astrocytesin 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.
Footnotes
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↵* This work was supported by Swedish Medical Research Council Projects 11548, 09041, and 03157; Swedish Cancer Foundation Project 3622; a fellowship from the Swedish Society for Medical Research (to M. P.); and grants from the Swedish Society for Medicine, the Swedish Society for Medical Research, the King Gustaf V Foundation, A+ Science Invest, Inga-Britt and Arne Lundberg Foundation, Göran Gustafsson Foundation, the Academy of Finland, and Turku Graduate School in Biomedical Sciences.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom all correspondence should be addressed: Dept. of Medical Biochemistry, University of Gothenburg, Box 440, SE-405 30 Gothenburg, Sweden. Fax: 46-31-416108; E-mail: Milos.Pekny@medkem.gu.se.
- Abbreviations:
- IF
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intermediate filament
- GFAP
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glial fibrillary acidic protein
- CNS
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central nervous system
- PAGE
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polyacrylamide gel electrophoresis
- IR
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immunoreactivity
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- Received March 23, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
