The CB₁ receptor interacts with cereblon and drives cereblon deficiency-associated memory shortfalls.

ABSTRACT: Cereblon/CRBN is a substrate-recognition component of the Cullin4A-DDB1-Roc1 E3 ubiquitin ligase complex. Destabilizing mutations in the human CRBN gene cause a form of autosomal recessive non-syndromic intellectual disability (ARNSID) that is modelled by knocking-out the mouse Crbn gene. A reduction in excitatory neurotransmission has been proposed as an underlying mechanism of the disease. However, the precise factors eliciting this impairment remain mostly unknown. Here we report that CRBN molecules selectively located on glutamatergic neurons are necessary for proper memory function. Combining various in vivo approaches, we show that the cannabinoid CB₁ receptor (CB₁R), a key suppressor of synaptic transmission, is overactivated in CRBN deficiency-linked ARNSID mo

SUBMITTER: Costas-Insua C 

PROVIDER: S-EPMC11018632 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature