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NANOPDICS SIGNED

Optoelectrical Dynamics of Ion channel Activation in Calcium Nanodomains

Total Cost €

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EC-Contrib. €

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Partnership

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 NANOPDICS project word cloud

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

protein    structural    pore    local    region    cellular    membrane    mode    specialized    rearrangements    vivo    function    subcellular    activation    adequately    genetics    isolated    signal    domain    complete    located    animal    created    critical    spectroscopy    sensing    ca2    variants    bk    underlying    tight    candidates    biochemistry    intracellular    position    dependent    synapses    channels    coupling    electrophysiology    excitability    laboratory    perfect    players    conductance    localization    environment    subunits    behavior    first    restricted    channel    crystallography    regulation    close    fluorescent    optimize    combination    time    act    sites    binding    synergistic    group    report    physiologically    molecular    gated    mechanism    nevertheless    measured    movements    vdcc    effectors    sensors    neuronal    accessory    accompanying    deploy    neurons    voltage    nm    separately    reporters    structures    depolarization    domains    optoelectrical    influx    functional    dynamics    nanodomains   

Project "NANOPDICS" data sheet

The following table provides information about the project.

Coordinator
UNIVERSIDAD DE LA LAGUNA 

Organization address
address: MOLINOS DE AGUA S/N
city: LA LAGUNA TENERIFE
postcode: 38071
website: http://www.ull.es

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 Spain [ES]
 Project website http://www.ull.es/molcan
 Total cost 1˙999˙742 €
 EC max contribution 1˙999˙742 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSIDAD DE LA LAGUNA ES (LA LAGUNA TENERIFE) coordinator 1˙999˙742.00

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 Project objective

In neurons, sites of Ca2 influx and Ca2 sensors are located within 20-50 nm, in subcellular “Ca2 nanodomains”. Such tight coupling is crucial for the functional properties of synapses and neuronal excitability. Two key players act together in nanodomains, coupling Ca2 signal to membrane potential: the voltage-dependent Ca2 channels (VDCC) and the large conductance Ca2 and voltage-gated K channels (BK). BK channels are characterized by synergistic activation by Ca2 and membrane depolarization, but the complex molecular mechanism underlying channel function is not adequately understood. Information about the pore region, voltage sensing domain or isolated intracellular domains has been obtained separately using electrophysiology, biochemistry and crystallography. Nevertheless, the specialized behavior of this channel must be studied in the whole protein complex at the membrane in order to determine the complete range of structures and movements critical to its in vivo function. Using a combination of genetics, electrophysiology and spectroscopy, our group has measured for the first time the structural rearrangements accompanying whole BK channel activation at the membrane. From this unique position, our first goal is to fully determine the real time structural dynamics underlying the molecular coupling of Ca2, voltage and activation of BK channels in the membrane environment, its regulation by accessory subunits and channel effectors. BK subcellular localization and role in Ca2 nanodomains make these channels perfect candidates as reporters of local changes in [Ca2] restricted to specific nanodomains close to the neuronal membrane. In our laboratory we have created fluorescent variants of the channel that report BK activity induced by Ca2 binding, or Ca2 binding and voltage. Our second aim in this proposal is to optimize and deploy this novel optoelectrical reporters to study physiologically relevant Ca2-induced processes both in cellular and animal mode

 Publications

year authors and title journal last update
List of publications.
2018 Aravind S. Kshatri, Alberto Gonzalez-Hernandez, Teresa Giraldez
Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System
published pages: , ISSN: 1662-5099, DOI: 10.3389/fnmol.2018.00258
Frontiers in Molecular Neuroscience 11 2020-04-15
2018 Pablo Miranda, Miguel Holmgren, Teresa Giraldez
Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.40664
eLife 7 2020-04-15
2020 A. Kshatri1,2, A. Cerrada1,2, R. Gimeno1,2, D. Bartolomé-Martín1,2, P. Rojas3 and T. Giraldez
Differential regulation of BK channels by fragile X mental retardation protein
published pages: , ISSN: , DOI:
The Journal of General Physiology 2020-04-15
2020 Elva Martin-Batista, Laura E. Maglio, Natalia Armas-Capote, Guadalberto Hernandez, Diego Alvarez de la Rosa, Teresa Giraldez
Neuronal kinase SGK1.1 protects against brain damage after status epilepticus
published pages: , ISSN: , DOI:
2020-04-15
2019 Natalia Armas-Capote, Laura E Maglio, Leonel Pérez-Atencio, Elva Martin-Batista, Antonio Reboreda, Juan A Barios, Guadalberto Hernandez, Diego Alvarez de la Rosa, José Antonio Lamas, Luis C Barrio, Teresa Giraldez
SGK1.1 Reduces Kainic Acid-Induced Seizure Severity and Leads to Rapid Termination of Seizures
published pages: , ISSN: 1047-3211, DOI: 10.1093/cercor/bhz302
Cerebral Cortex 2020-04-15
2018 Aravind S. Kshatri, Alberto J. Gonzalez-Hernandez, Teresa Giraldez
Functional validation of Ca 2+ -binding residues from the crystal structure of the BK ion channel
published pages: 943-952, ISSN: 0005-2736, DOI: 10.1016/j.bbamem.2017.09.023
Biochimica et Biophysica Acta (BBA) - Biomembranes 1860/4 2019-06-07
2017 Teresa Giraldez, Brad S. Rothberg
Understanding the conformational motions of RCK gating rings
published pages: 431-441, ISSN: 0022-1295, DOI: 10.1085/jgp.201611726
The Journal of General Physiology 149/4 2019-06-07
2016 Pablo Miranda, Teresa Giraldez, Miguel Holmgren
Interactions of divalent cations with calcium binding sites of BK channels reveal independent motions within the gating ring
published pages: 14055-14060, ISSN: 0027-8424, DOI: 10.1073/pnas.1611415113
Proceedings of the National Academy of Sciences 113/49 2019-06-07
2016 Teresa Giraldez
The GoSlo family of BK channel activators: A no-go for γ subunits?
published pages: 1-2, ISSN: 1933-6950, DOI: 10.1080/19336950.2016.1263136
Channels 2019-06-07

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