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Etude mécanistique des récepteurs P2X par l'utilisation de molécules photoisomérisables

Abstract : P2X receptors, activated by extracellular ATP and non-selective cations, are involved in many physiopathological roles. The lack of selectivity of pharmacological molecules is a major drawback for their study. The resolution of their crystallographic structures provided a molecular framework, but the mechanisms involved in allosteric transitions remain misunderstood. In the laboratory, two tools have been developed, derived from azobenzene, allowing the activation of P2X receptors in the absence of ATP and by light. The use of these tools allowed the study of the allosteric transition from the open to the desensitized state, highlighting an effective regulatory zone in transmembrane spaces. In addition, their use provided the biophysical investigation of a mutation present on hP2X2, responsible for non-syndromatic hearing loss. This mutation leads to a narrowing of the pore, affecting the large cations flow involved in hearing process. Finally, the relationship between the diameter of the ionic pore and the passage of large cations has been established.
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Juline Beudez. Etude mécanistique des récepteurs P2X par l'utilisation de molécules photoisomérisables. Neurosciences [q-bio.NC]. Université de Strasbourg, 2018. Français. ⟨NNT : 2018STRAJ084⟩. ⟨tel-02357343⟩

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