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GFAP at 50.

ABSTRACT: Fifty years have passed since the discovery of glial fibrillary acidic protein (GFAP) by Lawrence Eng and colleagues. Now recognized as a member of the intermediate filament family of proteins, it has become a subject for study in fields as diverse as structural biology, cell biology, gene expression, basic neuroscience, clinical genetics and gene therapy. This review covers each of these areas, presenting an overview of current understanding and controversies regarding GFAP with the goal of stimulating continued study of this fascinating protein.

SUBMITTER: Messing A

PROVIDER: S-EPMC7440737 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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GFAP at 50.

Messing Albee A Brenner Michael M

ASN neuro 20200101

Fifty years have passed since the discovery of glial fibrillary acidic protein (GFAP) by Lawrence Eng and colleagues. Now recognized as a member of the intermediate filament family of proteins, it has become a subject for study in fields as diverse as structural biology, cell biology, gene expression, basic neuroscience, clinical genetics and gene therapy. This review covers each of these areas, presenting an overview of current understanding and controversies regarding GFAP with the goal of sti ...[more]

PMID: 32811163

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Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice.

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| S-EPMC2665202 | biostudies-literature

GFAP?/GFAP? ratio directs astrocytoma gene expression towards a more malignant profile.

Project description:Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several GFAP splice variants have been identified and the main variants expressed in human astrocytoma are the GFAP? and GFAP? isoforms. Here we show a significant downregulation of GFAP? in grade IV astrocytoma compared to grade II and III, resulting in an increased GFAP?/? ratio. Mimicking this increase in GFAP?/? ratio in astrocytoma cell lines and comparing the subsequent transcriptomic changes with the changes in the patient tumours, we have identified a set of GFAP?/? ratio-regulated high-malignant and low-malignant genes. These genes are involved in cell proliferation and protein phosphorylation, and their expression correlated with patient survival. We additionally show that changing the ratio of GFAP?/?, by targeting GFAP expression, affected expression of high-malignant genes. Our data imply that regulating GFAP expression and splicing are novel therapeutic targets that need to be considered as a treatment for astrocytoma.

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Regulation of GFAP Expression.

Project description:Expression of the GFAP gene has attracted considerable attention because its onset is a marker for astrocyte development, its upregulation is a marker for reactive gliosis, and its predominance in astrocytes provides a tool for their genetic manipulation. The literature on GFAP regulation is voluminous, as almost any perturbation of development or homeostasis in the CNS will lead to changes in its expression. In this review, we limit our discussion to mechanisms proposed to regulate GFAP synthesis through a direct interaction with its gene or mRNA. Strengths and weaknesses of the supportive experimental findings are described, and suggestions made for additional studies. This review covers 15 transcription factors, DNA and histone methylation, and microRNAs. The complexity involved in regulating the expression of this intermediate filament protein suggests that GFAP function may vary among both astrocyte subtypes and other GFAP-expressing cells, as well as during development and in response to perturbations.

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Transgenic analysis of GFAP promoter elements.

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Astrocytoma cell lines transduced to either express GFAP isoforms or to knockdown GFAP isoforms

Project description:Modulation of the GFAP cytoskeleton in astrocytoma cells alters processes involved in extracellular matrix remodelling and cell-cell signalling – a transcriptome analysis Astrocytomas grade IV are malignant brain tumours with no effective treatment and a five year survival rate of only 5%. Expression of Glial Fibrillary Acidic Protein (GFAP) is lower in high astrocytoma grade, but the expression of the splice isoform GFAPδ is similar in low and high-grade astrocytomas. Thus the ratio of GFAPδ/α is increased in high-grade astrocytomas. We studied transcriptome changes in astrocytoma cell lines resulting from an induced alteration of GFAP isoform expression. GFAPα or GFAPδ were increased or decreased by recombinant expression or shRNA mediated knockdown of GFAPpan or GFAPα. We find that the most prominent effects are induced by the modulations where the GFAPδ/GFAPα ratio is increased. Gene ontology analysis revealed that the main effects of GFAP modulation take place in the extracellular matrix remodelling and cellular signalling clusters, with possible implications in astrocytoma invasive behaviour and angiogenesis.

2017-07-03 | GSE74567 | GEO

GFAP and its role in Alexander disease.

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GFAP transgenic mice expression analysis

Project description:Olfactory bulb transcript levels for GFAP transgenic mice compared to wildtype at 3wks and 4mos Keywords = GFAP Keywords = Rosenthal fibers Keywords = Alexander disease Keywords: other

2005-07-20 | GSE977 | GEO

Isolation and characterization of GFAP-positive porcine neural stem/progenitor cells derived from a GFAP-CreER<sup>T2</sup> transgenic piglet.

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Drug screening to identify suppressors of GFAP expression.

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