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1. Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

Author

Susanna Törnroth-Horsefield, Mootaz M. Salman, Andrea M. Halsey, Alex C. Conner, Jerome Badaut, Marie Xun Wang, Roslyn M. Bill, Jeffrey J. Iliff, Philip Kitchen, Centre de résonance magnétique des systèmes biologiques (CRMSB), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
Water flow, [SDV]Life Sciences [q-bio], Aquaporin, Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Homeostasis, Humans, 030304 developmental biology, Glia limitans, Aquaporin 4, 0303 health sciences, Neurodegeneration, Water, Subcellular localization, medicine.disease, medicine.anatomical_structure, Blood-Brain Barrier, Astrocytes, Glymphatic system, Neurology (clinical), sense organs, Neuroscience, 030217 neurology & neurosurgery, Astrocyte
Abstract

Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed in astrocytes. In the CNS, it is enriched in astrocyte endfeet, at synapses, and at the glia limitans, where it mediates water exchange across the blood–spinal cord and blood–brain barriers (BSCB/BBB), and controls cell volume, extracellular space volume, and astrocyte migration. Perivascular enrichment of AQP4 at the BSCB/BBB suggests a role in glymphatic function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease.

Published
2021
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2. Biomimetic water channels: general discussion

Author

Susanna Törnroth-Horsefield, Qilei Song, Bing Gong, Baoxia Mi, Bruce J. Hinds, Manish Kumar, Gerhard Hummer, Harish Vashisth, Mark S.P. Sansom, Philip A. Gale, Marc Baaden, Maria Di Vincenzo, Mahesh Lokesh, Roslyn M. Bill, Yves-Marie Legrand, Michael Fröba, Jeffery T. Davis, Martin Vögele, Mihail Barboiu, Robert J. Hickey, Claus Hélix-Nielsen, Jun li Hou, Viatcheslav Freger, Samuel Murail, Chun-Long Chen, Peter Pohl, Woochul Song, Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Department of Theoretical Biophysics [Frankfurt am Main], Max-Planck-Institut für Biophysik - Max Planck Institute of Biophysics (MPIBP), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, INFLIBNET Centre, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Université Paris Diderot - Paris 7 (UPD7)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)

Subjects
Materials science, [CHIM]Chemical Sciences, Nanotechnology, 02 engineering and technology, Physical and Theoretical Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 0210 nano-technology, 01 natural sciences, ComputingMilieux_MISCELLANEOUS, 0104 chemical sciences
Abstract

International audience

Published
2018
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3. Eukaryotic expression: developments for structural proteomics

Author

Albrecht Messerschmidt, Udo Heinemann, Simon J. Davis, S. Macieira, Tzviya Zeev-Ben-Mordehai, D Ksiazek, Yoav Peleg, Titia K. Sixma, Geoff Sutton, Klaus Maskos, Ian M. Jones, E Y Jones, G Schneider, Rene Assenberg, N Tarboureich, Arnaud Poterszman, Didier Busso, Joel L. Sussman, Lena Gustafsson, A R Aricescu, Christine Lang, Anastassis Perrakis, Veronica T. Chang, A Dubrovsky, Roslyn M. Bill, Kristina Hedfalk, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Proteomics, Glycosylation, MESH: Gene Expression, Saccharomyces cerevisiae, Gene Expression, MESH: Selenomethionine, Computational biology, high throughput, yeast, MESH: Eukaryotic Cells, mammalian cells, Pichia pastoris, 03 medical and health sciences, chemistry.chemical_compound, baculovirus, Structural Biology, Yeasts, Gene expression, Protein biosynthesis, Animals, MESH: Animals, MESH: Cloning, Molecular, Cloning, Molecular, Selenomethionine, Cells, Cultured, 030304 developmental biology, Cloning, 0303 health sciences, biology, MESH: Proteomics, MESH: Yeasts, 030302 biochemistry & molecular biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, biology.organism_classification, MESH: Glycosylation, Research Papers, eukaryotic expression, Yeast, Cell biology, Eukaryotic Cells, chemistry, MESH: Baculoviridae, Baculoviridae, MESH: Cells, Cultured
Abstract

The production of sufficient quantities of protein is an essential prelude to a structure determination, but for many viral and human proteins this cannot be achieved using prokaryotic expression systems. Groups in the Structural Proteomics In Europe (SPINE) consortium have developed and implemented high-throughput (HTP) methodologies for cloning, expression screening and protein production in eukaryotic systems. Studies focused on three systems: yeast (Pichia pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and transient expression in mammalian cells. Suitable vectors for HTP cloning are described and results from their use in expression screening and protein-production pipelines are reported. Strategies for co-expression, selenomethionine labelling (in all three eukaryotic systems) and control of glycosylation (for secreted proteins in mammalian cells) are assessed.

Published
2006
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