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VOLSIGNAL SIGNED

Volume regulation and extracellular signalling by anion channels

Total Cost €

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EC-Contrib. €

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Partnership

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 VOLSIGNAL project word cloud

Explore the words cloud of the VOLSIGNAL project. It provides you a very rough idea of what is the project "VOLSIGNAL" about.

physiological    gradients    osmolytes    disruption    putting    remarkable    organismal    remained    assumed    once    context    organic    faces    apoptosis    functions    osmotic    drive    heterogeneous    creates    released    ko    identity    epithelia    stagnated    membrane    depends    player    cl    extracellular    models    transport    whereas    physiology    channels    division    genes    sirna    anion    subunit    regulatory    lrrc8    drugs    signalling    identification    conditional    diverse    transepithelial    glutamate    migration    cells    missing    screens    structural    dissect    water    transporters    composition    ions    vrac    first    abolishes    breakthrough    osmolarity    ion    play    total    group    vracs    unknown    discovered    ground    roles    components    pathology    secondarily    discover    emboldened    molecules    biology    function    genome    brain    vesicle    channel    metabolites    purposes    search    regulate    serve    cell    heteromers    cellular    interactors    functionally    lrrc8a    surprising    break    regulated    exocytosis    abrogating    regulation    mice    physiologically    mouse    volume   

Project "VOLSIGNAL" data sheet

The following table provides information about the project.

Coordinator
FORSCHUNGSVERBUND BERLIN EV 

Organization address
address: RUDOWER CHAUSSEE 17
city: BERLIN
postcode: 12489
website: www.fv-berlin.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙499˙991 €
 EC max contribution 2˙499˙991 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FORSCHUNGSVERBUND BERLIN EV DE (BERLIN) coordinator 2˙499˙991.00

Map

 Project objective

Cells must regulate their volume in response to changes in osmolarity and during cell division, migration, apoptosis, and transepithelial transport. Regulated membrane transport of ions and metabolites creates osmotic gradients that secondarily drive water across the membrane. Organic ‘osmolytes’ such as glutamate also serve in extracellular signalling and volume-regulatory ion transporters are often used for other purposes, putting volume regulation into the context of diverse organismal functions.

Research on cell volume regulation stagnated because the identity of a key player, the Volume-Regulated Anion Channel VRAC, remained unknown. Very recently we identified LRRC8 heteromers as VRAC components and discovered that VRACs are a heterogeneous group of channels. Their remarkable ability to transport not only Cl-, but also signalling molecules or drugs, depends on their LRRC8 subunit composition. This breakthrough now allows us to search for functionally relevant interactors and to dissect the physiological roles of different VRACs using mouse models. Whereas disruption of Lrrc8a abolishes VRAC function, abrogating other Lrrc8 genes (in total five) will change its transport properties. Conditional KO mice will first focus on epithelia which faces large osmolarity changes, on the brain where VRAC-released signalling molecules are supposed to play important roles in physiology and pathology, and on VRAC’s assumed role in vesicle exocytosis. We expect to discover many surprising novel roles of VRACs.

Emboldened by our identification of VRAC, we will use genome-wide siRNA screens to identify two other ‘missing’ ion channels, which have been known physiologically for many years and may have widespread roles in signalling and other physiological processes. Once identified, these channels will be studied at a structural, cellular and organismal level.

These projects will break new ground in physiology, cell biology, signalling and pathology.

 Publications

year authors and title journal last update
List of publications.
2019 Florian Ullrich, Sandy Blin, Katina Lazarow, Tony Daubitz, Jens Peter von Kries, Thomas J Jentsch
Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.49187
eLife 8 2020-01-30
2018 Till Stuhlmann, Rosa Planells-Cases, Thomas J. Jentsch
LRRC8/VRAC anion channels enhance β-cell glucose sensing and insulin secretion
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-04353-y
Nature Communications 9/1 2019-06-06
2018 Jennifer C. Lück, Dmytro Puchkov, Florian Ullrich, Thomas J. Jentsch
LRRC8/VRAC anion channels are required for late stages of spermatid development in mice
published pages: 11796-11808, ISSN: 0021-9258, DOI: 10.1074/jbc.RA118.003853
Journal of Biological Chemistry 293/30 2019-06-06
2018 Pingzheng Zhou, Maya M. Polovitskaya, Thomas J. Jentsch
LRRC8 N termini influence pore properties and gating of volume-regulated anion channels (VRACs)
published pages: 13440-13451, ISSN: 0021-9258, DOI: 10.1074/jbc.ra118.002853
Journal of Biological Chemistry 293/35 2019-06-06

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