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

• Main Authors: Xia-Jing Tong, Zhitao Hu, Yu Liu, Dorian Anderson, Joshua M Kaplan
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2015-11-01
• Series: eLife
• Subjects: autism; synaptic transmission; GABA-A receptors; CASK; neurexin; neuroligin
• Online Access: https://elifesciences.org/articles/09648

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.