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Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior.

ABSTRACT: Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CA1 region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1? (protein phosphase 1?)-P-Rex1-Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CA1 region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CA1 LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs.

SUBMITTER: Li J

PROVIDER: S-EPMC4687539 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior.

Li Jun J Chai Anping A Wang Lifang L Ma Yuanlin Y Wu Zhiliu Z Yu Hao H Mei Liwei L Lu Lin L Zhang Chen C Yue Weihua W Xu Lin L Rao Yi Y Zhang Dai D

Proceedings of the National Academy of Sciences of the United States of America 20151130 50

Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CA1 region of the hippocampus in mice resulted in au ...[more]

PMID: 26621702

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Dataset Information

Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior.

Publications

Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior.

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