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From structure to disease: the evolving tale of aquaporin biology

Nature Reviews Molecular Cell Biology volume 5, pages 687–698 (2004)Cite this article

Key Points

  • Aquaporins are membrane-channel proteins that are present at all levels of life, from bacteria to mammals. Most aquaporins are selectively permeated by water, although some family members are permeated by other small molecules.

  • Aquaporins are present in the membrane as tetramers. Each aquaporin monomer contains its own channel.

  • Structural studies have elucidated the molecular basis for channel selectivity, and are likely to provide insights into the mechanisms by which some members of the family are gated.

  • Eleven mammalian aquaporins have been identified so far and they have cellular and subcellular distributions in different organs that indicate probable functional roles. Studies in animals and humans have revealed that aquaporins participate in a wide range of physiological and pathological processes.

  • Aquaporin regulation across the protein family is complex. It includes transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

  • The discovery of aquaporins provoked a reconsideration of the mechanisms that underlie the water permeability of membranes. Recognition that membrane water permeability might be regulated independently of solute permeability has provided new insights into organ physiology, and might lead to the identification of aquaporins as targets for novel therapies in pathological conditions in which water homeostasis is disrupted.

Abstract

Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins — the aquaporins. These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. The recognition of aquaporins has stimulated a reconsideration of membrane water permeability by investigators across a wide range of disciplines.

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Figure 1: The aquaporin family tree.
Figure 2: The structure of aquaporin-1.
Figure 3: Aquaporin distribution in the human kidney.
Figure 4: Aquaporin distribution in the human respiratory tract.
Figure 5: Aquaporin distribution in the human eye.
Figure 6: Aquaporin expression in brain astrocytes.

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Acknowledgements

The authors receive support from the National Heart, Lung and Blood Institute (L.S.K. and P.A.) and the National Eye Institute (P.A.) of the National Institutes of Health, USA, and from the American Heart Association (L.S.K.).

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  1. Department of Medicine, Division of Pulmonary and Critical Care Medicine, and the Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, 21224, Maryland, USA

    Landon S. King, David Kozono & Peter Agre

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  1. Landon S. King
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DATABASES

Entrez

AqpZ

GlpF

Interpro

PDZ domain

OMIM

autosomal dominant NDI

autosomal recessive NDI

Sjögren's syndrome

Protein Data Bank

1J4N

Swiss-Prot

AQP0

AQP1

AQP2

AQP3

AQP4

AQP5

AQP6

AQP7

AQP8

AQP9

AQP10

Glossary

FREEZE–FRACTURE

A technique that allows the examination of membrane proteins by first freezing and then fracturing a tissue to separate the inner and outer leaflets of the membrane bilayer. This technique can be particularly useful for the examination of integral membrane proteins and cell junctions.

DIPOLE

A pair of equal and opposite electrical charges that are located only a short distance apart, for example, at either end of a small molecule.

SERUM OSMOLALITY

A measure of the solute concentration in a particular solution, including biological solutions such as blood or urine. The units for osmolality are milliosmoles of solute per kg of solvent (mosmol kg−1).

TUBULOGLOMERULAR FEEDBACK

The process by which increased fluid and solute delivery out of the proximal tubule feeds back to reduce glomerular filtration and to limit the loss of urine volume.

PNEUMOCYTES

In common usage, this term is applied to the two principal epithelial cell types that line the alveoli of the lungs. Type-I pneumocytes are large flat cells, and type-II pneumocytes are cuboidal cells.

OSMOTIC WATER PERMEABILITY

The permeability of a membrane to water in response to an osmotic gradient across the membrane.

HYDROSTATIC PERMEABILITY

The permeability of a membrane in response to a pressure gradient across the membrane.

OEDEMA

Excess fluid in a particular tissue or anatomic compartment. Swelling in the legs and excess fluid in the airspaces of the lung are examples of oedema.

CATARACTS

Opacities in the lens of the eye that are formed by precipitated proteins or degraded cells and that markedly decrease vision by interfering with the passage of light through the lens.

SCLERAL FIBROBLASTS

Fibroblasts that are found in the sclera, the tissue that forms the white part of the eye.

KERATINOCYTES

Epithelial cells of the skin that have differentiated to produce keratin. Keratinocytes are the predominant cell type in the epidermis of the skin.

TRABECULAR MESHWORK

An anatomic structure at the outer border of the anterior chamber of the eye. This structure consists of a network of endothelial-cell-covered strands that resorb the liquid that is found in the anterior chamber of the eye (aqueous humor).

CANALS OF SCHLEMM

Tubular channels in the eye that are found at the junction of the cornea and sclera, and through which aqueous humor drains.

MYOEPITHELIAL CELLS

Contractile epithelial-like cells that function like smooth muscle, but are usually found between secretory cells and the basement membrane in glands. They have long cytoplasmic extensions, which contain actin bands that can contract to facilitate fluid movement out of the secretory gland.

CHOROID PLEXUS

A collection of villous-like processes at select sites in the ventricular system of the brain. These processes contain a special secretory epithelium that secretes cerebrospinal fluid.

CYSTIC FIBROSIS TRANSMEMBRANE-CONDUCTANCE REGULATOR

(CFTR). This protein forms a chloride channel, is present in many tissues including the lung, kidney and pancreas, and is mutated in cystic fibrosis.

GLUCONEOGENESIS

The process by which glucose is made from amino acids or glycerol in the fasting state. This process occurs primarily in the liver.

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King, L., Kozono, D. & Agre, P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5, 687–698 (2004). https://doi.org/10.1038/nrm1469

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