Cytoskeletal Anchoring of GLAST Determines Susceptibility to Brain Damage
Open accessAbstract
Glial fibrillary acidic protein (GFAP) is an enigmatic protein; it currently has no unambiguously defined role. It is expressed in the cytoskeleton of astrocytes in the mammalian brain. We have used co-immunoprecipitation to identify in vivo binding partners for GFAP in the rat and pig brain. We demonstrate interactions between GFAP, the glutamate transporter GLAST, the PDZ-binding protein NHERF1, and ezrin. These interactions are physiologically relevant; we demonstrate in vitro that transport of D-aspartate (a glutamate analogue) is significantly increased in the presence of GFAP and NHERF1. Moreover, we demonstrate in vivo that expression of GFAP is essential in retaining GLAST in the plasma membranes of astrocytes after an hypoxic insult. These data indicate that the cytoskeleton of the astrocyte plays an important role in protecting the brain against glutamate-mediated excitotoxicity.
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Adequate GFAP expression is necessary for retaining GLAST in the plasma membrane.
“adequate GFAP expression is necessary for retaining GLAST in the plasma membrane [36].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [36]
The Discussion (page unavailable) reports that increased GFAP expression coincided with GLAST retention in astrocyte processes after hypoxia, and Figure 6 shows GLAST in the plasma membrane of a GFAP-labeled astrocyte. These observations support an association, but they do not establish that adequate GFAP expression is necessary to retain GLAST in the plasma membrane. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAstroglial reactivity impacts astrocyte-dependent glutamate homeostasis.
“As astroglial reactivity impacts astrocyte‐dependent glutamate homeostasis [36, 94, 95, 96, 97]”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [36]
Under prolonged stress it can result in chronical inflammation.
“under prolonged stress it can result in chronical inflammation [20, 36, 105, 109].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [36]
The Discussion describes astrocyte and GLAST changes after hypoxia, not chronic inflammation caused by prolonged stress. Searches for prolonged stress and chronic inflammation, including inflammatory responses to sustained hypoxia, found no passage addressing that claim. (LLM, conf=0.72)
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- Authors
- Sullivan, S. M., Lee, A., Björkman, S. T., Miller, S. M., Sullivan, R. K. P., Poronnik, P., Colditz, P. B., & Pow, D. V.
- Affiliations
- University of Newcastle Australia (AU)
- The University of Queensland (AU)
- Corresponding author
- Pow, David V.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 282
- Issue
- 40
- Pages
- 29414-29423
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041340250
- Cited by
- 128
- References
- 0
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 1 · 2020: 9 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 8
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- glial fibrillary acidic protein, GLAST, glutamate transporters, NHERF1, ezrin, protein-protein interaction, hypoxia, excitotoxicity, brain damage, plasma membrane retention
- MeSH terms
- Ezrin, Animals, Biological Transport, Brain, Cytoskeletal Proteins, Cytoskeleton, Glial Fibrillary Acidic Protein, Humans, Microscopy, Fluorescence, Models, Biological, Swine, Transfection, D-Aspartic Acid, Excitatory Amino Acid Transporter 1, Mice, Rats
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