Molecular mechanisms governing aquaporin relocalisation

Andrea Markou; Lucas Unger; Mohammed Abir-awan; Ahmed Saadallah; Andrea Halsey; Zita Balklava; Matthew Conner; Susanna Törnroth-horsefield; Stuart D. Greenhill; Alex Conner; Roslyn M. Bill; Mootaz M. Salman; Philip Kitchen

doi:10.1016/j.bbamem.2021.183853

Molecular mechanisms governing aquaporin relocalisation

Andrea Markou, Lucas Unger, Mohammed Abir-awan, Ahmed Saadallah, Andrea Halsey, Zita Balklava, Matthew Conner, Susanna Törnroth-horsefield, Stuart D. Greenhill, Alex Conner, Roslyn M. Bill, Mootaz M. Salman, Philip Kitchen

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	183853
Journal	BBA -Biomembranes
Volume	1864
Issue number	4
Early online date	30 Dec 2021
DOIs	https://doi.org/10.1016/j.bbamem.2021.183853
Publication status	Published - 1 Apr 2022

Bibliographical note

© 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).

Keywords

AQP
Aquaporin
Membrane trafficking
Osmosis

Access to Document

10.1016/j.bbamem.2021.183853Licence: CC BY 4.0

Molecular mechanisms governing aquaporin relocalisation
© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license 4.0
Final published version, 2.03 MBLicence: CC BY 4.0

Cite this

@article{2f7b4692019345d1942eb0deff76e722,

title = "Molecular mechanisms governing aquaporin relocalisation",

abstract = "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.",

keywords = "AQP, Aquaporin, Membrane trafficking, Osmosis",

author = "Andrea Markou and Lucas Unger and Mohammed Abir-awan and Ahmed Saadallah and Andrea Halsey and Zita Balklava and Matthew Conner and Susanna T{\"o}rnroth-horsefield and Greenhill, {Stuart D.} and Alex Conner and Bill, {Roslyn M.} and Salman, {Mootaz M.} and Philip Kitchen",

note = "{\textcopyright} 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{\textquoteleft}s Horizon 2020 research and innovation programme under Marie Sk{\l}odowska 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).",

year = "2022",

month = apr,

day = "1",

doi = "10.1016/j.bbamem.2021.183853",

language = "English",

volume = "1864",

journal = "BBA -Biomembranes",

issn = "0005-2736",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Molecular mechanisms governing aquaporin relocalisation

AU - Markou, Andrea

AU - Unger, Lucas

AU - Abir-awan, Mohammed

AU - Saadallah, Ahmed

AU - Halsey, Andrea

AU - Balklava, Zita

AU - Conner, Matthew

AU - Törnroth-horsefield, Susanna

AU - Greenhill, Stuart D.

AU - Conner, Alex

AU - Bill, Roslyn M.

AU - Salman, Mootaz M.

AU - Kitchen, Philip

N1 - © 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).

PY - 2022/4/1

Y1 - 2022/4/1

N2 - 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.

AB - 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.

KW - AQP

KW - Aquaporin

KW - Membrane trafficking

KW - Osmosis

UR - https://linkinghub.elsevier.com/retrieve/pii/S0005273621003011

UR - http://www.scopus.com/inward/record.url?scp=85123175947&partnerID=8YFLogxK

U2 - 10.1016/j.bbamem.2021.183853

DO - 10.1016/j.bbamem.2021.183853

M3 - Article

SN - 0005-2736

VL - 1864

JO - BBA -Biomembranes

JF - BBA -Biomembranes

IS - 4

M1 - 183853

ER -

Molecular mechanisms governing aquaporin relocalisation

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Deciphering The Role Of Gtpases And The Cytoskeleton In Aquaporin-4 Vesicular Trafficking

Cite this

Molecular mechanisms governing aquaporin relocalisation

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Student theses

Deciphering The Role Of Gtpases And The Cytoskeleton In Aquaporin-4 Vesicular Trafficking

Cite this