Aquaporin water channels in the nervous system

Key Points

  • Aquaporins (AQPs) are water channel proteins that increase cell membrane water permeability and assemble in cell membranes as tetramers.

  • AQP4, the main water channel in the CNS, is expressed in astrocytes and facilitates the formation and elimination of CNS oedema, modulates neuronal excitability and enhances astrocyte migration.

  • AQP4 also has a role in sensory perception, including vision, hearing and olfaction.

  • Autoantibodies against AQP4 cause neuromyelitis optica, an inflammatory demyelinating disease of the CNS.

  • Aquaporins are also expressed in the peripheral and enteric nervous systems, although their functions at these sites are not known.

Abstract

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage.

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Figure 1: Sequence and structural features of AQP4.
Figure 2: Aquaporin expression in the nervous system.
Figure 3: Routes of water flow into and out of the CNS in brain oedema.
Figure 4: Aquaporin 4 involvement in astrocyte migration and neuroexcitation.
Figure 5: Proposed role of aquaporin 4 in the pathogenesis of neuromyelitis optica.

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Acknowledgements

Our research is funded by the US National Institutes of Health and the Guthy-Jackson Charitable Foundation. We thank S. Saadoun for providing helpful criticism of the manuscript.

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Glossary

α-syntrophin

An intracellular protein that may form a complex with aquaporin 4.

Agrin

A proteoglycan attached to extracellular matrix that may anchor aquaporin 4 in the membrane.

Glial-limiting membrane

This is the interface between the brain and the surrounding cerebrospinal fluid, and comprises astrocyte processes.

Circumventricular organs

These are regions of the brain near ventricles that lack the blood–brain barrier.

Choroid plexus

An intraventricular epithelial structure that secretes cerebrospinal fluid.

Tanycytes

These are elongated cells that project from the third ventricle to the hypothalamus.

Ruffini mechanoreceptors

These are skin mechanoreceptors.

Müller cells

These are aquaporin 4-expressing retinal glial cells.

Claudius cells

These are supporting cells (non-excitable cells) in the inner ear.

Hensen cells

These are supporting cells (non-excitable cells) in the inner ear.

Inner sulcus cells

These are supporting cells (non-excitable cells) in the inner ear.

Cytotoxic oedema

This is the intracellular accumulation of excess water (cell-swelling oedema).

Vasogenic oedema

This is the interstitial accumulation of excess brain water (leaky-vessel oedema).

Ependyma

A membrane of epithelial cells lining the ventricles.

Kaolin

This is aluminium silicate that causes obstructive hydrocephalus when injected into the cisterna magna of rodents.

Lamellipodia

Projections at the front end of a migrating cell.

Glioblastoma multiforme

This is a highly infiltrative, malignant tumour of astrocytes.

C5b–C9 complexes

Cell plasma membrane pores composed of the complement proteins C5b, C6, C7, C8 and C9. Deposition of enough pores causes cell lysis.

Plasma blast

Upon activation by T helper cells, B cells differentiate into plasma cells that secrete high levels of antibody. Plasma blasts are the most immature plasma cells.

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Papadopoulos, M., Verkman, A. Aquaporin water channels in the nervous system. Nat Rev Neurosci 14, 265–277 (2013). https://doi.org/10.1038/nrn3468

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