New ion channel families
par- 6 mai 2010
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 controled by P2X2-evoked calcium influx.
2- Physiological and pathological implication. 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.
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