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Review
. 2020 Jul 2;9(7):1604.
doi: 10.3390/cells9071604.

The Diversity of Intermediate Filaments in Astrocytes

Maja Potokar  1   2 , Mitsuhiro Morita  3 , Gerhard Wiche  2   4 , Jernej Jorgačevski  1   2
Affiliations
Review

The Diversity of Intermediate Filaments in Astrocytes

Maja Potokar et al. Cells. .

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.

Keywords: GFAP; astrocytes; cytolinker proteins; intermediate filaments; nestin; plectin; reactive gliosis; synemin; vimentin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cellular distribution of GFAP and vimentin cytoskeleton in primary rat astrocytes in normal conditions and in conditions that are typically present in pathological states. Astrocytes treated with dbcAMP (N 6,2′-O -dibutyryladenosine 3′:5′ cyclic monophosphate), a membrane-permeable analogue of cAMP, mimic general reactive gliosis. Hypotonic stimulation, on the other hand, leads readily to astrocyte swelling, which is a part of the cytotoxic or cellular edema response. Changes in intracellular arrangement of vimentin (A) and GFAP (B) filaments are evident in reactive astrocytes (after cAMP stimulation) and after hypotonic stimulation (HYPO), as revealed by immunolabeling. Note also the stellated morphology of astrocytes after the increase in cAMP. Hypotonic treatment triggered depolymerization of vimentin filaments—selected areas (white squares) are magnified (2×)—in insets Bars: 10 µm. Modified with permission from [84] (Regulation of AQP4 Surface Expression via Vesicle Mobility in Astrocytes, GLIA, Copyright© 2013 Wiley Periodicals, Inc., (Hoboken, NJ, USA)).
Figure 2
Figure 2
Expression profile of intermediate filament and cytolinker genes in A1 and A2 reactive astrocytes. Microarray data provided in [98] are converted to Z scores and expressed as a heatmap. Saline-1 to -4 are controls of LPS treatments (A1 reactive astrocytes) and sham-1 to -4 are controls of MCAO (A2 reactive astrocytes), where LPS is Escherichia coli endotoxin O55:B55 and MCAO stands for transient ischaemia induced by occluding the middle cerebral artery. H2-T23 and Serping 1 are representative genes highly and selectively expressed in the A1 astrocyte subtype, whereas Clcf1 and Tgm 1 are specific for the A2 astrocyte subtype.
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