Aquaporin Biology in Membrane Transport Systems

Aquaporins are integral membrane proteins that mediate rapid, selective water transport across cellular bilayers in response to osmotic gradients. Each aquaporin monomer forms a narrow aqueous pore, and functional channels assemble as tetramers or higher-order oligomers. These proteins are expressed in diverse tissues—kidney, brain, glandular epithelia and other organs—where they underpin processes including fluid secretion, waste removal and tissue homeostasis. Beyond canonical water channels (AQP1, AQP2, AQP4, AQP5), aquaglyceroporins (AQP3, AQP7, AQP9) facilitate glycerol and small solute permeability, linking membrane transport to metabolic regulation. Recent structural insights have revealed arrangements such as the inter-tetrameric interfaces that modulate junction-like functions in endocrine tissues. Functionally, aquaporins contribute to urine concentration, salivary secretion, bile formation, central nervous system water balance and tumour cell motility. Dysregulation of isoform expression or subcellular localisation underlies pathologies including brain oedema, hydrocephalus, cholestasis, cancer invasion and metabolic disorders. Emerging data also highlight roles in the glymphatic clearance of metabolites from the brain and potential as therapeutic targets for oedema and oncological indications.

Research from Nature Portfolio

Recent studies have elucidated the high-resolution structure of human AQP7 in its octameric assembly, revealing two adhering tetramers stabilised by extracellular loops that form a central pore with dual leucine constriction sites. The structure, determined by single-particle cryo-EM at 2.55 Å resolution, uncovers glycerol 3-phosphate occupancy in the central pore and suggests that AQP7 not only serves as a glycerol channel but also may function as a junctional protein in pancreatic islet cells. The identification of this inter-tetrameric interface advances understanding of how aquaglyceroporins can integrate channel and adhesion roles, with implications for metabolic regulation in endocrine tissues.

Aquaporin Biology in Membrane Transport Systems publication trend

The graph below shows the total number of articles in aquaporin biology in membrane transport systems across all publications each year (not limited to Nature Index journals).

Technical terms

Aquaporin: A class of membrane channel proteins that selectively facilitate water transport across lipid bilayers.

Aquaglyceroporin: A subfamily of aquaporins permeable to glycerol and small neutral solutes as well as water.

Osmotic gradient: A difference in solute concentration across a membrane that drives water movement.

Cryo-EM: Cryogenic electron microscopy, a structural biology technique used to determine high-resolution structures of protein complexes.

Tetramer: An oligomeric assembly of four protein subunits, typical of functional aquaporin channels.

Glymphatic system: A brain-wide pathway for fluid and metabolite clearance reliant on AQP4 expression in astrocyte endfeet.

References

1. Hepatic Bile Formation: Developing a New Paradigm. Pharmacological Reviews (2023).
2. Cryo-EM structure supports a role of AQP7 as a junction protein. Nature Communications (2023).
3. Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema. Cell (2020).
4. Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease. Cells (2019).
5. Regulation of AQP4 in the Central Nervous System. International Journal of Molecular Sciences (2020).
6. Defective Secretion of Saliva in Transgenic Mice Lacking Aquaporin-5 Water Channels*. Journal of Biological Chemistry (1999).
7. Molecular structure of the water channel through aquaporin CHIP. The hourglass model.. Journal of Biological Chemistry (1994).
8. Severely Impaired Urinary Concentrating Ability in Transgenic Mice Lacking Aquaporin-1 Water Channels*. Journal of Biological Chemistry (1998).
9. Molecular Characterization of a Broad Selectivity Neutral Solute Channel*. Journal of Biological Chemistry (1998).