NEW ION CHANNEL FAMILIES
Department: Neurosciences - Research axis: Biology of ion channels

Research subject

Adenosine triphosphate (ATP) is the molecule, which in all organisms provides energy necessary for biochemical reactions. In vertebrates, ATP is also an extracellular signaling molecule that binds to two different families of plasma membrane receptors. Our team is involved in the characterization of one of these family, the P2X receptors. Seven P2X receptors have been identified. They form a ionic pore in the membrane, which opens upon ATP binding, allowing calcium entry into the cell. P2X receptors are expressed in numerous tissues, particularly in immune and neuronal cells.

The team focuses on two main aspects of P2X receptor biology:

1-Molecular characterization. We investigate the interaction of P2X receptors with intracellular proteins in order to get a better insight of the intracellular pathways regulated by these receptors. We have found that P2X2 interact specifically with a intracellular calcium sensor protein. In neurons, this interaction is dynamically regulated by neuronal activity and controlled by P2X2-evoked calcium influx.

2-We are also investigating the assembly at the plasma membrane of P2X subunits. We have developed a Bioluminescente Resonance Energy Transfer (BRET) assay which allows to  decipher the specificity and the stoichiometry of P2X subunit assembly. We have characterized a new heteromeric P2X receptor made by the association of P2X2 and P2X5 subunits. This receptor present properties close to that of the P2X7 receptors, particularly regarding its permeability dynamics.

3-Physiological and pathological functions. Through the generation of genetically modified mice, we are investigating the physiological role of P2X receptors and their implication in pathology. Our results demonstrated that the P2X4 receptor is involved in synaptic plasticity, a molecular form of learning and memory. We have also demonstrated that this receptor is involved in the development of different forms of chronic pain as well as in communication between immune cells and neurons. Our results show that several P2X receptors are potential therapeutic targets in the treatment of inflammation and neurodegenerative disorders. Lately, we focused on the role of P2X receptor signalling in microglial functions.

Our team is part of the LabEX Ion Channel Science and Therapeutics: http://www.labex-icst.fr/en

 

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Team

Team leader

François Rassendren
DR2, CNRS


  IGF Nord 207c

  04 34 35 92 85

 

Staff

Maxime Bonnet
Master 2, CNRS


  IGF Nord 207b

  04 34 35 92 85

 

Vincent Compan
CRCN, Inserm


  IGF Nord 207c

  04 34 35 92 85

 

Anne-Laure Hemonnot
Doctorant(e), UM


  IGF Nord 207c

  04 34 35 92 85

 

Hélène Hirbec
CRCN, CNRS


  IGF Nord 207b

  04 34 35 93 04

 

Jennifer Hua
Doctorant(e), CNRS


  IGF Nord 207a

  04 34 35 93 04

 

Nathalie Linck
AI, UM


  IGF Nord 207b

  04 34 35 93 04

 

Matthias Ollivier
Doctorant(e), CNRS


  IGF Nord 207c

  04 34 35 93 04

 

Eloïse Pascal
Master 1, CNRS


  IGF Nord 207a

  04 34 35 92 85

 

Lauriane Ulmann
MCF, UM


  IGF Nord 207c

  04 34 35 93 04

 


Major publications

  • Ventre E, Rozières A, Lenief V, Albert F, Rossio R, Laoubi L, Dombrowicz D, Staels B, Ulmann L, Julia V, Vial E, Jomard A, Hacini Rachinel F, Nicolas JFand Vocanson M. Allergy, 2017, 72(8):1212-1221
  • Compan V, Pierredon S, Vanderperre B, Krznar P, Marchiq I, Zamboni N, Pouyssegur J, Martinou JC (2015). Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect. Mol Cell. 59:491-501
  • Compan V, Martín-Sánchez F, Baroja-Mazo A, López-Castejón G, Gomez AI, Verkhratsky A, Brough D, Pelegrín P (2015), Apoptosis-associated speck-like protein containing a CARD forms specks but does not activate caspase-1 in the absence of NLRP3 during macrophage swelling. J Immunol. 194:1261-73.
  • Baroja-Mazo A, Martín-Sánchez F, Gomez AI, Martínez CM, Amores-Iniesta J, Compan V, Barberà-Cremades M, Yagüe J, Ruiz-Ortiz E, Antón J, Buján S, Couillin I, Brough D, Arostegui JI, Pelegrín P (2014). The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response. Nat Immunol. 15:738-48.
  • Compan V, Baroja-Mazo A, López-Castejón G, Gomez AI, Martínez CM, Angosto D, Montero MT, Herranz AS, Bazán E, Reimers D, Mulero V, Pelegrín P (2012). Cell volume regulation modulates NLRP3 inflammasome activation. Immunity. 37:487-500.
  • Compan V, Baroja-Mazo A, Bragg L, Verkhratsky A, Perroy J, Pelegrin P. A genetically encoded IL-1β bioluminescence resonance energy transfer sensor to monitor inflammasome activity (2012). J Immunol. 189:2131-7.
  • Rassendren F and Audinat E (2016) Purinergic signaling in epilepsy. J NeurosciRes. 94:781-793.
  • Mounira S, Fontanaud P, Linck N, Boussadia B, Peyroutou R, Lasgouzes T, Rassendren F, Marchi N, Hirbec H (2016) Evidence for status epilepticus and pro-inflammatory changes after intranasal kainic acid administration in mice. PLoS ONE 11(3): e0150793. doi:10.1371/ journal.pone.0150793. 
  • Sendin G, Bourien J, Rassendren F, Puel JL, Nouvian R (2014) Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea. Proc. Natl. Acad. Sci. USA 111:1999-2004
  • Lemoine D, Habermacher C, Martza A, Méry P-F, Bouquier N, Diverchy F, Taly A, Rassendren F, Specht A and Grutter T (2013) Optical control of an ion channel gate. Proc. Natl. Acad. Sci. USA 110:20813-20818.
  • Ulmann L, Levavasseur F, Avignone E, Peyroutou R, Hirbec H, Audinat E, Rassendren F. (2013) Involvement of P2X4 receptors in hippocampal microglial activation after Status Epilepticus. Glia 61 : 1306-1319
  • Compan V, Ulmann L, Stelmashenko O, Chemin J, Chaumont S, Francois Rassendren (2012) P2X2 and PX5 subunits define a new heteromeric receptor with P2X7 like properties. J Neurosci. 32 :4284-96.
  • Ulmann L, Hirbec H, Rassendren F (2010) P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain. Embo J 29:2290-2300.
  • Ulmann L, Hatcher JP, Hughes JP, Chaumont S, Green PJ, Conquet F, Buell GN, Reeve AJ, Chessell IP, Rassendren F (2008) Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J Neurosci 28:11263-11268.
  • Avignone E, Ulmann L, Levavasseur F, Rassendren F, Audinat E (2008) Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling. J Neurosci 28:9133-9144.
  • Chaumont S, Compan V, Toulme E, Richler E, Housley GD, Rassendren F, Khakh BS (2008) Regulation of P2X2 receptors by the neuronal calcium sensor VILIP1. Sci Signal 1:ra8

 

 

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