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
|
PII |
e09648
|
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
|
Resource |
C.elegans |
|