Journal article
Neurexins Physically and Functionally Interact with GABA A Receptors
Neuron (Cambridge, Mass.), Vol.66(3), pp.403-416
2010
DOI: 10.1016/j.neuron.2010.04.008
PMID: 20471353
Abstract
Neurexins are presynaptic cell-adhesion molecules that form
trans-synaptic complexes with postsynaptic neuroligins. When overexpressed in nonneuronal cells, neurexins induce formation of postsynaptic specializations in cocultured neurons, suggesting that neurexins are synaptogenic. However, we find that when overexpressed in neurons, neurexins do not increase synapse density, but instead selectively suppressed GABAergic synaptic transmission without decreasing GABAergic synapse numbers. This suppression was mediated by all subtypes of neurexins tested, in a cell-autonomous and neuroligin-independent manner. Strikingly, addition of recombinant neurexin to cultured neurons at submicromolar concentrations induced the same suppression of GABAergic synaptic transmission as neurexin overexpression. Moreover, experiments with native brain proteins and purified recombinant proteins revealed that neurexins directly and stoichiometrically bind to GABA
A receptors, suggesting that they decrease GABAergic synaptic responses by interacting with GABA
A receptors. Our findings suggest that besides their other well-documented interactions, presynaptic neurexins directly act on postsynaptic GABA
A receptors, which may contribute to regulate the excitatory/inhibitory balance in brain.
► Neurexin overexpression decreases inhibitory but not excitatory synaptic strength ► Neurexins do not induce or depress synapse formation ► Extracellular domains of neurexins and GABA receptors directly interact ► Neurexins freeze activation of GABAergic synapses via this receptor interaction
Details
- Title: Subtitle
- Neurexins Physically and Functionally Interact with GABA A Receptors
- Creators
- Chen Zhang - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USADeniz Atasoy - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USADemet Araç - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USAXiaofei Yang - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USAMarc V Fucillo - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USAAlfred J Robison - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USAJaewon Ko - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USAAxel T Brunger - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USAThomas C Südhof - Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USA
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.66(3), pp.403-416
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.neuron.2010.04.008
- PMID
- 20471353
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Language
- English
- Date published
- 2010
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040010102771
Metrics
30 Record Views