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      The Diversity of Intermediate Filaments in Astrocytes

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          Abstract

          Despite the remarkable complexity of the individual neuron and of neuronal circuits, it has been clear for quite a while that, in order to understand the functioning of the brain, the contribution of other cell types in the brain have to be accounted for. Among glial cells, astrocytes have multiple roles in orchestrating neuronal functions. Their communication with neurons by exchanging signaling molecules and removing molecules from extracellular space takes place at several levels and is governed by different cellular processes, supported by multiple cellular structures, including the cytoskeleton. Intermediate filaments in astrocytes are emerging as important integrators of cellular processes. Astrocytes express five types of intermediate filaments: glial fibrillary acidic protein (GFAP); vimentin; nestin; synemin; lamins. Variability, interactions with different cellular structures and the particular roles of individual intermediate filaments in astrocytes have been studied extensively in the case of GFAP and vimentin, but far less attention has been given to nestin, synemin and lamins. Similarly, the interplay between different types of cytoskeleton and the interaction between the cytoskeleton and membranous structures, which is mediated by cytolinker proteins, are understudied in astrocytes. The present review summarizes the basic properties of astrocytic intermediate filaments and of other cytoskeletal macromolecules, such as cytolinker proteins, and describes the current knowledge of their roles in normal physiological and pathological conditions.

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          Most cited references183

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          CNS stem cells express a new class of intermediate filament protein.

          Multipotential CNS stem cells receive and implement instructions governing differentiation to diverse neuronal and glial fates. Exploration of the mechanisms generating the many cell types of the brain depends crucially on markers identifying the stem cell state. We describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells. The predicted amino acid sequence of the nestin gene product shows that nestin defines a distinct sixth class of intermediate filament protein. These observations extend a model in which transitions in intermediate filament gene expression reflect major steps in the pathway of neural differentiation.
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            Tripartite synapses: glia, the unacknowledged partner.

            According to the classical view of the nervous system, the numerically superior glial cells have inferior roles in that they provide an ideal environment for neuronal-cell function. However, there is a wave of new information suggesting that glia are intimately involved in the active control of neuronal activity and synaptic neurotransmission. Recent evidence shows that glia respond to neuronal activity with an elevation of their internal Ca2+ concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength. In view of these new insights, this article suggests that perisynaptic Schwann cells and synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses.
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              GFAP in health and disease.

              Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein in mature astrocytes, but also an important component of the cytoskeleton in astrocytes during development. Major recent developments in astrocyte biology and the discovery of novel intermediate filament functions enticed the interest in the function of GFAP. The discovery of various GFAP splice variants gave an additional boost to explore this protein in more detail. The structural role of GFAP in astrocytes has been widely accepted for a long time, but over the years, GFAP has been shown to be involved in astrocyte functions, which are important during regeneration, synaptic plasticity and reactive gliosis. Moreover, different subpopulations of astrocytes have been identified, which are likely to have distinctive tasks in brain physiology and pathology, and which are not only classified by their spatial and temporal appearance, but also by their specific expression of intermediate filaments, including distinct GFAP isoforms. The presence of these isoforms enhances the complexity of the astrocyte cytoskeleton and is likely to underlie subtype specific functions. In this review we discuss the versatility of the GFAP cytoskeletal network from gene to function with a focus on astrocytes during human brain development, aging and disease. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                02 July 2020
                July 2020
                : 9
                : 7
                : 1604
                Affiliations
                [1 ]Laboratory of Neuroendocrinology – Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia; maja.potokar@ 123456mf.uni-lj.si
                [2 ]Celica BIOMEDICAL, 1000 Ljubljana, Slovenia; gerhard.wiche@ 123456univie.ac.at
                [3 ]Department of Biology, Kobe University Graduate School of Science, Kobe 657-8501, Japan; mmorita@ 123456boar.kobe-u.ac.jp
                [4 ]Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria
                Author notes
                [* ]Correspondence: jernej.jorgacevski@ 123456mf.uni-lj.si ; Tel.: +386-(1)-543-7081
                Author information
                https://orcid.org/0000-0001-9550-5463
                https://orcid.org/0000-0003-3550-2011
                Article
                cells-09-01604
                10.3390/cells9071604
                7408014
                32630739
                40abc2c1-8eca-457e-9eb7-e2fbdb1338de
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 June 2020
                : 01 July 2020
                Categories
                Review

                astrocytes,intermediate filaments,gfap,vimentin,nestin,synemin,plectin,cytolinker proteins,reactive gliosis

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