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

• DOI: 10.1016/j.isci.2022.105467
• Publication Date: 2022-10-30T02:52:17Z
• Authors: Zaha Merlaud; Xavier Marques; Marion Russeau; Ursula Saade; Maelys Tostain; Imane Moutkine; Marc Gielen; Pierre-Jean Corri...; Sabine Lévi
• Keywords: Gephyrin; Neurotransmitter receptor

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