Biology of ion channels

TREK1 potassium ion channels fluorescing green in these cultured neurons

Ion channels generate the electrical signals with which the nervous system senses the world, processes information, creates memories and controls behavior. One of the most diverse and important families of ion channels, the K2P potassium channels, serves as a hub for the generation and regulation of the negative resting membrane potential and neuronal excitability. K2P channels also play a central role in the response of cells to extracellular and intracellular signals as diverse as GPCR signaling, pH, and membrane stretch.

TREK1 potassium ion channels fluorescing green in these cultured neurons

Probing of ion channel function requires pharmacological agents or gene invalidation (KO mice) to be addressed. However, selective ligands are lacking for many neuronal signaling proteins, including K2P channels. Due to this limitation, gene inactivation has been the main approach to study the physiological roles of several proteins, including K2P TREK channels. However, KO mice, while useful for a rough characterization of a genes function, have many disadvantages for deciphering a precise role for a gene, including gene redundancy and developmental issues. To overcome these limitations, we recently developed light-gated versions of members K2P subfamilies (notably TREKlight, a TREK1 K2P channel that is regulated by light). These light-gated channels allow to remote control of neuronal activity and to study channel pharmacology. From these channels, we also developed an important new method for optogenetics, which we called the photoswitched conditional subunit method (TREK1-PCS), which makes it possible to endow native (unmodified) channels with sensitivity to light allowing their functional study.

TREKlight: a light gated TREK1 channel
TREKlight: a light gated TREK1 channel

 

We are now focusing on the following projects:

  • Study TREK K 2P channels physiology ex vivo by using TREK-PCS.
  • Development of a new animal model that will present the advantage of the ability to close TREK channels with light instantaneously and reversibly with both temporal and spatial precision to address the function of the channel in vivo
  • Development of new optical tools to allow remote control of protein functions

 

TREKlight, for remote control of neuronal activity
TREKlight, for remote control of neuronal activity

 

Last publications

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications. - 2016 - eLife - 5 - Harb K, Magrinelli E, Nicolas CS, Lukianets N, Frangeul L, Pietri M, Sun T, Sandoz G, Grammont F, Jabaudon D, Studer M, and Alfano,C

Heterodimerization within the TREK channel subfamily produces a diverse family of highly regulated potassium channels. - 2016 - Proceedings of the National Academy of Sciences of the United States of America - Levitz J, Royal P, Comoglio Y, Wdziekonski B, Schaub S, Clemens DM, Isacoff EY, and Sandoz,G

Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid. - 2014 - Proceedings of the National Academy of Sciences of the United States of America - Comoglio Y, Levitz J, Kienzler MA, Lesage F, Isacoff EY, and Sandoz,G

Mycobacterial toxin induces analgesia in buruli ulcer by targeting the angiotensin pathways. - 2014 - Cell - 157 P1565-76 - Marion E, Song OR, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V, Guérineau NC, Saint André JP, Gersbach P, Altmann KH, Stinear TP, Comoglio Y, Sandoz G, Preisser L, Delneste Y, Yeramian E, Marsollier L, and Brodin,P

Baclofen and Other GABAB Receptor Agents Are Allosteric Modulators of the CXCL12 Chemokine Receptor CXCR4. - 2013 - J Neurosci - 33 P11643-11654 - Guyon A, Kussrow A, Olmsted IR, Sandoz G, Bornhop DJ, and Nahon,JL

Optogenetic techniques for the study of native potassium channels. - 2013 - Front Mol Neurosci - 6 P6 - Sandoz G, and Levitz,J

Optical control of endogenous proteins with a photoswitchable conditional subunit reveals a role for TREK1 in GABA(B) signaling. - 2012 - Neuron - 74 P1005-14 - Sandoz G, Levitz J, Kramer RH, and Isacoff,EY

Molecular regulations governing TREK and TRAAK channel functions. - 2011 - Channels (Austin) - 5 P402-9 - No J, l G, Sandoz F, and Lesage,

A modern ionotropic glutamate receptor with a K(+) selectivity signature sequence. - 2011 - Nat Commun - 2 P232 - Janovjak H, Sandoz G, and Isacoff,EY

Optical probing of a dynamic membrane interaction that regulates the TREK1 channel. - 2011 - Proc Natl Acad Sci U S A - 108 P2605-10 - Sandoz G, Bell SC, and Isacoff,EY

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Sandoz Guillaume
Group Leader

2012 ATIP-AVENIR

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Members Team
PreDocs
   Avalos Prado Pablo
   Royal Perrine
Engineers & Technicians
   Wdziekonski Brigitte
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    September 2013 - G. Sandoz Team
   1 POST-DOC position   Closed

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