title: A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors.
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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Xia-Jing
authors.initials: XJ
authors.lastname: Tong
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Dorian
authors.initials: D
authors.lastname: Anderson
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009469:Neuromuscular Junction / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015816:Cell Adhesion Molecules, Neuronal; D011963:Receptors, GABA-A
keywords: C. elegans; CASK; GABA-A receptors; autism; neurexin; neuroligin; neuroscience; synaptic transmission