» Articles » PMID: 20471353

Neurexins Physically and Functionally Interact with GABA(A) Receptors

Overview
Journal Neuron
Publisher Cell Press
Specialty Neurology
Date 2010 May 18
PMID 20471353
Citations 102
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Resolving native GABA receptor structures from the human brain.

Zhou J, Noviello C, Teng J, Moore H, Lega B, Hibbs R Nature. 2025; 638(8050):562-568.

PMID: 39843743 DOI: 10.1038/s41586-024-08454-1.


Advances in the labelling and selective manipulation of synapses.

Timalsina B, Lee S, Kaang B Nat Rev Neurosci. 2024; 25(10):668-687.

PMID: 39174832 DOI: 10.1038/s41583-024-00851-9.


GABA receptors and neuroligin 2 synergize to promote synaptic adhesion and inhibitory synaptogenesis.

Sui Y, Mortensen M, Yuan B, Nicholson M, Smart T, Jovanovic J Front Cell Neurosci. 2024; 18:1423471.

PMID: 39100896 PMC: 11295144. DOI: 10.3389/fncel.2024.1423471.


Neuronal and non-neuronal functions of the synaptic cell adhesion molecule neurexin in Nematostella vectensis.

Guzman C, Mohri K, Nakamura R, Miyake M, Tsuchiya Y, Tomii K Nat Commun. 2024; 15(1):6495.

PMID: 39090098 PMC: 11294457. DOI: 10.1038/s41467-024-50818-8.


Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.

Sanfilippo P, Kim A, Bhukel A, Yoo J, Mirshahidi P, Pandey V Neuron. 2024; 112(6):942-958.e13.

PMID: 38262414 PMC: 10957333. DOI: 10.1016/j.neuron.2023.12.014.


References
1.
Ko J, Zhang C, Arac D, Boucard A, Brunger A, Sudhof T . Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation. EMBO J. 2009; 28(20):3244-55. PMC: 2771087. DOI: 10.1038/emboj.2009.249. View

2.
Missler M, Fernandez-Chacon R, Sudhof T . The making of neurexins. J Neurochem. 1998; 71(4):1339-47. DOI: 10.1046/j.1471-4159.1998.71041339.x. View

3.
Patzke H, Ernsberger U . Expression of neurexin Ialpha splice variants in sympathetic neurons: selective changes during differentiation and in response to neurotrophins. Mol Cell Neurosci. 2000; 15(6):561-72. DOI: 10.1006/mcne.2000.0853. View

4.
Comoletti D, Flynn R, Boucard A, Demeler B, Schirf V, Shi J . Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for beta-neurexins. Biochemistry. 2006; 45(42):12816-27. DOI: 10.1021/bi0614131. View

5.
Kattenstroth G, Tantalaki E, Sudhof T, Gottmann K, Missler M . Postsynaptic N-methyl-D-aspartate receptor function requires alpha-neurexins. Proc Natl Acad Sci U S A. 2004; 101(8):2607-12. PMC: 356997. DOI: 10.1073/pnas.0308626100. View