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Elife. 2015 Nov 17;4:e09648. doi: 10.7554/eLife.09648.

A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors.

Tong XJ1,2, Hu Z1,2, Liu Y1,2, Anderson D1,2, Kaplan JM1,2.

Author information

1
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, United States.
2
Department of Neurobiology, Harvard Medical School, Boston, United States.

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.

KEYWORDS:

C. elegans; CASK; GABA-A receptors; autism; neurexin; neuroligin; neuroscience; synaptic transmission

PMID:
26575289
PMCID:
PMC4642926
DOI:
10.7554/eLife.09648
[Indexed for MEDLINE]
Free PMC Article

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