RRC ID 53503
Author Tong XJ, Hu Z, Liu Y, Anderson D, Kaplan JM.
Title A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors.
Journal Elife
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.
Volume 4
Pages e09648
Published 2015-11-17
DOI 10.7554/eLife.09648
PMID 26575289
PMC PMC4642926
MeSH Animals Autistic Disorder / genetics Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Adhesion Molecules, Neuronal / genetics Cell Adhesion Molecules, Neuronal / metabolism* Gene Expression Regulation* Humans Neuromuscular Junction / genetics* Neuromuscular Junction / metabolism* Protein Binding Receptors, GABA-A / genetics Receptors, GABA-A / metabolism*
IF 7.551
Times Cited 20