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

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.

Review: Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder

“…Outside the central nervous system, AQP4 is expressed and localized at the basolateral membrane of epithelial cells in the kidneys, gastrointestinal organs, airways and skeletal muscles. However, the pathological changes seen in patients with NMOSD rarely occur in these AQP4‐expressing peripheral tissues . Recent studies suggest that the relatively low involvement and varying degrees of injury to peripheral organs may be related to the different distributions of the AQP4 isoforms and the expression of several membrane‐bound complement regulators in these organs .…”

Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy

“…In the human hippocampus, AQP4 has been found in the Cornu Ammonis (CA) and dentate gyrus (DG) areas. At the cellular and subcellular level, AQP4 is abundantly expressed in the plasma membrane of the astrocytes that sheathe the glutamatergic synapses and shows the highest expression in perivascular astrocytes, where it is localised to the plasma membrane of astrocytic end-feet at the glia limitans (Lee et al, 2004;Gleiser et al, 2016). AQP4 is co-localised with inwardly rectifying K + channels (Kir4.1) and glial K + uptake is attenuated in AQP4 knockout mice compared to wild-type, indicating a functional interaction (Padmawar et al, 2005;Binder et al, 2006Binder et al, , 2012.…”

Expression of aquaporins in inner ear disease

“…AQP4 belongs to the CAQP subfamily and has been found in many organs since it was first discovered in the brain. AQP4 plays a role in maintaining the water balance of the central nervous system . According to studies using human tissue microarrays, AQP4 was found most frequently in the cerebral cortex, cerebellar cortex, ependymal cell layer, hippocampus, and spinal cord .…”

“…According to studies using human tissue microarrays, AQP4 was found most frequently in the cerebral cortex, cerebellar cortex, ependymal cell layer, hippocampus, and spinal cord . In addition, it has been shown to be expressed in kidneys, salivary glands, and intestines as well as in the sensory organs retina, olfactory epithelium, and organ of Corti . Expression was found to be high in sensory cells, such as those associated with hearing, vision, and taste in zebrafish, but not in nonsensory cells .…”