The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis.
© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license 4.0
Funding: MB, ACC and PK were supported by the Biotechnology & Biosciences Research Council (BB/P025927/1). LU is supported by the European Union‘s Horizon 2020 research and innovation programme under Marie Skłodowska Curie grant agreement No. 847,419 (MemTrain). MA is supported by a studentship co-funded by Aston University and the UK Engineering and Physical Sciences Research Council (EP/R512889/1) to RMB. AS is supported by a studentship from the Iraqi Ministry of Higher Education and Scientific Research and the University of Mosul. AH was supported by a studentship from Spinal Research. STH is supported by the Swedish Research Council (2013-05945), the Crafoord Foundation (20140811 and 20180916) and the Magnus Bergvall Foundation (2015-01534).
- Membrane trafficking