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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.

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

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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