A network of autism linked genes stabilizes two pools of synaptic GABAA receptors

eLife

Dorian Anderson¹  Zhitao Hu¹  Joshua M Kaplan²  Xia-Jing Tong²  Yu Liu² 

[1] Department of Neurobiology, Harvard Medical School, Boston, United States;Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States;

关键词: autism;    synaptic transmission;    GABA-A receptors;    CASK;    neurexin;    neuroligin;   

DOI  :  10.7554/eLife.09648

来源: DOAJ

【 摘 要 】

Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD.

【 授权许可】

Unknown