Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease

Kim Wagner; Lucas Unger; Mootaz M. Salman; Philip Kitchen; Roslyn Bill; Andrea J. Yool

doi:10.3390/ijms23031388

Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease

Kim Wagner, Lucas Unger, Mootaz M. Salman, Philip Kitchen, Roslyn Bill^*, Andrea J. Yool^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

Abstract

The aquaporins (AQPs) are a family of small integral membrane proteins that facilitate the bidirectional transport of water across biological membranes in response to osmotic pressure gradients as well as enable the transmembrane diffusion of small neutral solutes (such as urea, glycerol, and hydrogen peroxide) and ions. AQPs are expressed throughout the human body. Here, we review their key roles in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. Evidence from a wide variety of studies now supports a view of the functions of AQPs being much more complex than simply mediating the passive flow of water across biological membranes. The discovery and development of small-molecule AQP inhibitors for research use and therapeutic development will lead to new insights into the basic biology of and novel treatments for the wide range of AQP-associated disorders.

Original language	English
Article number	1388
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	3
DOIs	https://doi.org/10.3390/ijms23031388
Publication status	Published - 26 Jan 2022

Bibliographical note

© 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

Funding: This work was supported by the Australian Research Council (grant number 19ARC_DP190
101745 to A.J.Y.), the UK Biotechnology and Biological Sciences Research Council (grant number
BB/P025927/1 to R.M.B. and P.K.), the European Union’s Horizon 2020 Research and Innovation
Programme under Marie Sklodowska Curie, grant agreement No. 847,419 (MemTrain; a studentship
to L.U.), an Aston University 50th Anniversary Fellowship (to P.K.), and GOstralia! PhD scholarship
support (to K.W.).

Keywords

Aquaporin (AQP)
Facilitated diffusion
Fluid
Membranes
Osmosis
Secretion
Signaling
Water

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10.3390/ijms23031388Licence: CC BY 3.0

Signaling Mechanisms and Pharmacological Modulators
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Final published version, 4.21 MBLicence: CC BY 3.0

Cite this

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title = "Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease",

abstract = "The aquaporins (AQPs) are a family of small integral membrane proteins that facilitate the bidirectional transport of water across biological membranes in response to osmotic pressure gradients as well as enable the transmembrane diffusion of small neutral solutes (such as urea, glycerol, and hydrogen peroxide) and ions. AQPs are expressed throughout the human body. Here, we review their key roles in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. Evidence from a wide variety of studies now supports a view of the functions of AQPs being much more complex than simply mediating the passive flow of water across biological membranes. The discovery and development of small-molecule AQP inhibitors for research use and therapeutic development will lead to new insights into the basic biology of and novel treatments for the wide range of AQP-associated disorders.",

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author = "Kim Wagner and Lucas Unger and Salman, {Mootaz M.} and Philip Kitchen and Roslyn Bill and Yool, {Andrea J.}",

note = "{\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Funding: This work was supported by the Australian Research Council (grant number 19ARC_DP190 101745 to A.J.Y.), the UK Biotechnology and Biological Sciences Research Council (grant number BB/P025927/1 to R.M.B. and P.K.), the European Union{\textquoteright}s Horizon 2020 Research and Innovation Programme under Marie Sklodowska Curie, grant agreement No. 847,419 (MemTrain; a studentship to L.U.), an Aston University 50th Anniversary Fellowship (to P.K.), and GOstralia! PhD scholarship support (to K.W.). ",

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AU - Bill, Roslyn

AU - Yool, Andrea J.

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N2 - The aquaporins (AQPs) are a family of small integral membrane proteins that facilitate the bidirectional transport of water across biological membranes in response to osmotic pressure gradients as well as enable the transmembrane diffusion of small neutral solutes (such as urea, glycerol, and hydrogen peroxide) and ions. AQPs are expressed throughout the human body. Here, we review their key roles in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. Evidence from a wide variety of studies now supports a view of the functions of AQPs being much more complex than simply mediating the passive flow of water across biological membranes. The discovery and development of small-molecule AQP inhibitors for research use and therapeutic development will lead to new insights into the basic biology of and novel treatments for the wide range of AQP-associated disorders.

AB - The aquaporins (AQPs) are a family of small integral membrane proteins that facilitate the bidirectional transport of water across biological membranes in response to osmotic pressure gradients as well as enable the transmembrane diffusion of small neutral solutes (such as urea, glycerol, and hydrogen peroxide) and ions. AQPs are expressed throughout the human body. Here, we review their key roles in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. Evidence from a wide variety of studies now supports a view of the functions of AQPs being much more complex than simply mediating the passive flow of water across biological membranes. The discovery and development of small-molecule AQP inhibitors for research use and therapeutic development will lead to new insights into the basic biology of and novel treatments for the wide range of AQP-associated disorders.

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KW - Membranes

KW - Osmosis

KW - Secretion

KW - Signaling

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ER -

Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease

Abstract

Bibliographical note

Keywords

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