Research
Role of TRP channels in cell physiology
Our laboratory studies the mechanisms regulating Ca2+ fluxes between intracellular medium, endoplasmic reticulum (ER), mitochondria and extracellular medium. In particular, we focused our research on TRP (Transient Receptor Potential) ion channels. Besides deciphering the gating mechanisms and the pharmacological properties of these channels, we try to understand their involvement in muscle contraction, in cell migration, proliferation and in apoptotic cell death. Recently, we began to investigate their role in brain, in particular in learning and memory processes.
TRP channels
TRP cationic channels constitute a large family of almost ubiquitously expressed proteins. The family was designated TRP because of a spontaneously occurring mutation in Drosophila, the photoreceptors of which lacked TRP protein and responded to a continuous light stimulus with a transient receptor potential response. The homologous proteins in mammalian cells seem to mediate cellular responses to a large variety of extracellular signals such as agonists, pheromones, odorant ligands, temperature, pH, osmolarity, oxidative stress.... Some isoforms also seem to be activated by depletion of intracellular Ca2+-stores. The activation and regulation mechanisms of TRP channels are largely unknown and diverse. On the basis of amino acids homologies, the mammalian TRP channel superfamily can be divided into six subfamilies: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPA1 (Ankyrin), TRPP (Polycystin) and TRPML (Mucolipin).
Ongoing projects are:
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TRPC and memory
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Mechanosensitivity of TRP channels
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Store-operated Ca2+ entry (SOCE) and cancer
Main publications (see here for complete list)
TRP Store-operated and mechanosensitive channels in skeletal muscle
Vandebrouck C., Martin D., Colson-Van Schoor M., Debaix H., Gailly P. (2002) Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. Journal of Cell Biology 158, 1089-1096.
Zanou N, Mondin L, Fuster C, Seghers F, Dufour I, Marie De Clippele M, Schakman O, Tajeddine N, Iwata Y, Wakabayashi S, Voets T, Allard B, Gailly P. (2015) Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres. Journal of Physiology 593(17), 3849-63.
TRPV4, a mechanosensitive channels in the kidney
Seghers F, Yerna X, Zanou N, Devuyst O, Vennekens R, Nilius B, Gailly P. (2016) TRPV4 participates in pressure-induced inhibition of renin secretion by juxtaglomerular cells. Journal of Physiology 594(24), 7327-7340.
Gualdani R, Seghers F, Yerna X, Schakman O, Tajeddine N, Achouri Y, Tissir F, Devuyst O, Gailly P. (2020) Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells. Science Signaling, Vol. 13, Issue 653, eabc6967 doi: 10.1126/scisignal.abc6967
TRP channels in cancer cells
Tajeddine N, Gailly P. (2012) TRPC1 channel is a major regulator of EGFR signaling. Journal of Biological chemistry 287, 16146-16157.
S., Zanou N., Yerna X., Emeriau N., Dufour I., Masquelier J., Muccioli G., Tajeddine N., Gailly P. (2016) Sphingosine-1-phosphate-activated TRPC1 channel controls chemotaxis of glioblastoma cells. Cell Calcium 60(6), 373-383.
Gualdani R, De Clippele M, Ratbi I, Gailly P, Tajeddine N. (2019) Store-Operated Calcium Entry Contributes to Cisplatin-Induced Cell Death in Non-Small Cell Lung Carcinoma. Cancers (Basel). 11(3). pii: E430. doi: 10.3390/cancers11030430.
TRPC channels and memory
Lepannetier S, Gualdani R, Tempesta S, Schakman O, Seghers F, Kreis A, Yerna X, Slimi A, de Clippele M, Tajeddine N, Voets T, Bon RS, Beech DJ, Tissir F, Gailly P (2018). Activation of TRPC1 channel by metabotropic glutamate receptor mGluR5 modulates synaptic plasticity and spatial working memory. Frontiers in Cellular Neuroscience 12, 318. doi: 10.3389/fncel.2018.00318.
Yerna X, Schakman O, Ratbi I, Kreis A, Lepannetier S, De Clippele M, Achouri Y, Tajeddine N, Tissir F, Gualdani R, Gailly P. (2020) Role of the TRPC1 Channel in Hippocampal Long-Term Depression and in Spatial Memory Extinction. International Journal of Molecular Sciences 21(5), 1712; doi:10.3390/ijms21051712
2018 activity report (extract) 
Contacts:Philippe Gailly - Principal investigator Tel: +32 2 764 55 42 Email: philippe.gailly@uclouvain.be - nicolas.tajeddine@uclouvain.be |