Structural basis of GABARAP-mediated GABA_A receptor trafficking and functions on GABAergic synaptic transmission.

ABSTRACT: GABA_A receptors (GABA_ARs) are the primary fast inhibitory ion channels in the central nervous system. Dysfunction of trafficking and localization of GABA_ARs to cell membranes is clinically associated with severe psychiatric disorders in humans. The GABARAP protein is known to support the stability of GABA_ARs in synapses, but the underlying molecular mechanisms remain to be elucidated. Here, we show that GABARAP/GABARAPL1 directly binds to a previously unappreciated region in the γ2 subunit of GABA_AR. We demonstrate that GABARAP functions to stabilize GABA_ARs via promoting its trafficking pathway instead of blocking receptor endocytosis. The GABARAPL1-γ2-GABA_AR crystal structure reveals the mechanisms underlying th

SUBMITTER: Ye J 

PROVIDER: S-EPMC7803741 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature