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Review
. 2016 Aug 26;17(9):1411.
doi: 10.3390/ijms17091411.

Aquaporin-4 in Astroglial Cells in the CNS and Supporting Cells of Sensory Organs-A Comparative Perspective

Corinna Gleiser  1 , Andreas Wagner  2 , Petra Fallier-Becker  3 , Hartwig Wolburg  4 , Bernhard Hirt  5 , Andreas F Mack  6
Affiliations
Review

Aquaporin-4 in Astroglial Cells in the CNS and Supporting Cells of Sensory Organs-A Comparative Perspective

Corinna Gleiser et al. Int J Mol Sci. .

Abstract

The main water channel of the brain, aquaporin-4 (AQP4), is one of the classical water-specific aquaporins. It is expressed in many epithelial tissues in the basolateral membrane domain. It is present in the membranes of supporting cells in most sensory organs in a specifically adapted pattern: in the supporting cells of the olfactory mucosa, AQP4 occurs along the basolateral aspects, in mammalian retinal Müller cells it is highly polarized. In the cochlear epithelium of the inner ear, it is expressed basolaterally in some cells but strictly basally in others. Within the central nervous system, aquaporin-4 (AQP4) is expressed by cells of the astroglial family, more specifically, by astrocytes and ependymal cells. In the mammalian brain, AQP4 is located in high density in the membranes of astrocytic endfeet facing the pial surface and surrounding blood vessels. At these locations, AQP4 plays a role in the maintenance of ionic homeostasis and volume regulation. This highly polarized expression has not been observed in the brain of fish where astroglial cells have long processes and occur mostly as radial glial cells. In the brain of the zebrafish, AQP4 immunoreactivity is found along the radial extent of astroglial cells. This suggests that the polarized expression of AQP4 was not present at all stages of evolution. Thus, a polarized expression of AQP4 as part of a control mechanism for a stable ionic environment and water balanced occurred at several locations in supporting and glial cells during evolution. This initially basolateral membrane localization of AQP4 is shifted to highly polarized expression in astrocytic endfeet in the mammalian brain and serves as a part of the neurovascular unit to efficiently maintain homeostasis.

Keywords: astroglial evolution; brain water channel; polarization; water homeostasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Freeze fracture replica of rat brain tissue surrounding a capillary: the fracture plane goes through the lumen (L) of a capillary and the bordering endothelial cell (End). This is surrounded by astrocytes A1 and A2. The membrane of A1 indicated by the square is shown at higher magnification in b; (b) High densities of orthogonal arrays of particles (OAP) are found on astrocytic endfeet facing a basal lamina. The circled area is magnified further showing OAPs on the P-face (Pf) If: intermediate filaments; (c) Ependymal cells lining the ventricle; and (d), hippocampal astrocytes in rat brain stained for glial fibrillary acidic protein (GFAP, red) and AQP4 (green). Ependymal cells are positive for AQP4 at their basolateral membranes, bearing cilia apically (arrows). Brain astrocytes in d show high AQP4 binding at their endfeet surrounding capillaries (arrows). Scale bars: (a) 1 µm; (b) 0.1 µm; (c) 5 µm; (d) 20 µm; (a,b) are modified from [24].
Figure 2
Figure 2
AQP4 immunocytochemical stains (red) in rodent sensory organs. (a) Rat olfactory region shows supporting epithelal cells and cells of Bowman’s glands positively stained. Receptor cells labelled by antibodies against the RNA-binding proteins HuC/D as a neuronal marker (green) are negative for AQP4; (b) AQP4 in the mouse retina is especially strong around blood vessels (arrows) but immunoreactivity is also present along the Müller cell processes and even at the outer limiting membrane (arrow heads). ONL: outer nuclear layer, INL: inner nuclear layer, GCL: ganglion cell layer; (c) AQP4 immunolabeling in the rat cochlear duct: In the medial part of the cochlear duct AQP4 was localized in the inner sulcus cells, and in the lateral part of the cochlear duct in Hensen’s cells and Claudius cells. The supporting cells of the organ of Corti were devoid of labeling for AQP4. The interdental cells and outer sulcus cells were out of focal plane. In c′–c′′′′ detailed confocal images of the subcellular AQP4 expression in the rat cochlear duct are shown: (c′) In the medial part of the cochlear duct AQP4 is localized in the basolateral membranes of the interdental cells; (c′′) the basal membrane domains of the inner sulcus cells (arrow head), and the basolateral membrane domains of the inner sulcus cells directly adjacent the organ of Corti (arrow); (c′′′) In the lateral part of the cochlear duct AQP4 is localized in the basolateral membrane domains of Hensen’s cells (arrow); and (c′′′′) the basal membranes of Claudius cells (arrow head). The outer sulcus cells with their root process show AQP4 expression in the basolateral membrane domains (arrow). Dotted lines represent the localization of inner hair cells, dashed lines mark outer hair cells. Scale bars represent 20 µm in all images.
Figure 3
Figure 3
AQP4 localization fish brain and retina. (a) Immunostain in the brain (optic tectum) of a zebrafish (Danio rerio). AQP4 is expressed along radial glial fibers, but not particularly enhanced at the brain surface nor around blood vessels; (b) In the retina of the cichlid fish Astatotilapia burtoni punctate stain for AQP4 is detected along Müller cell fibers and endfeet at the inner limiting membrane (arrow heads); (c) Freeze fracture electron micrograph through Müller cell endfeet facing a basal lamina (BL). The square area shown at higher magnification in the lower panel reveals OAPs (circled). INL: inner nuclear layer, GCL: ganglion cell layer, NFL: nerve fiber layer. Scale bars 20 µm in (a,b), and 0.5 µm and 0.1 µm in (c).
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