Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors

• Published in: Frontiers in bioscience (Landmark. Print) 2021-08, Vol.26 (8), p.335-346
• Main Authors: Wang, Xiaoya, Xu, Man, Xu, Qingbao, Yang, Feng, Tang, Hui, Shao, Chuan, Wang, Luyi, Wang, Yan, Deng, Jing, Wang, Shali
• Format: Article
• Language: English
• Subjects: Animals; autism; Autistic Disorder - genetics; Catenins - genetics; ctnnd2 gene; Hippocampus; learning and memory; Mice; Mice, Inbred C57BL; Mice, Knockout; mtor signaling; Neuronal Plasticity; Rapamycin-Insensitive Companion of mTOR Protein - genetics; rictor; Spatial Learning
• ISSN: 2768-6701; 2768-6698
• DOI: 10.52586/4947

: The gene which encodes a δ-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of in spatial cognition and related mechanisms remains obscure. : In this study, we generated a new line of -Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. : -KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both -KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of -KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. : The gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the gene in cognition at the molecular and synaptic levels.