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© Marie Prévost, Institut Pasteur
Image of a portion of a Xenopus oocyte expressing a channel receptor.
Publication : iScience

Conformational state-dependent regulation of GABAA receptor diffusion and subsynaptic domains.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in iScience - 18 Nov 2022

Merlaud Z, Marques X, Russeau M, Saade U, Tostain M, Moutkine I, Gielen M, Corringer PJ, Lévi S,

Link to Pubmed [PMID] – 36388998

Link to DOI – 10546710.1016/j.isci.2022.105467

iScience 2022 Nov; 25(11): 105467

The efficacy of GABAergic synapses relies on the number of postsynaptic GABAA receptors (GABAARs), which is regulated by a diffusion capture mechanism. Here, we report that the conformational state of GABAARs influences their membrane dynamics. Indeed, pharmacological and mutational manipulations of receptor favoring active or desensitized states altered GABAAR diffusion leading to the disorganization of GABAAR subsynaptic domains and gephyrin scaffold, as detected by super-resolution microscopy. Active and desensitized receptors were confined to perisynaptic endocytic zones, and some of them were further internalized. We propose that following their activation or desensitization, synaptic receptors rapidly diffuse at the periphery of the synapse where they remain confined until they switch back to a resting state or are internalized. We speculate that this allows a renewal of activatable receptors at the synapse, contributing to maintain the efficacy of the synaptic transmission, in particular on sustained GABA transmission.

https://pubmed.ncbi.nlm.nih.gov/36388998