A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26575289.
- Also identified by DOI 10.7554/eLife.09648 and PMC identifier 4642926.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 GABA(A) receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABA(A) receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABA(A) 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.
Medical subject headings
- Caenorhabditis elegans
- Cell Adhesion Molecules, Neuronal
- Gene Expression Regulation
- Neuromuscular Junction
- Receptors, GABA-A