Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex

Chih, Ben; Gollan, Leora; Scheiffele, Peter

doi:10.1016/j.neuron.2006.06.005

Cited by 394Neuroscience and Neuropharmacology ResearchRNA Research and SplicingGenetics and Neurodevelopmental Disorders

Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex

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Chih, Ben, Gollan, Leora, Scheiffele, Peter·2006·Neuron

DOI 10.1016/j.neuron.2006.06.005

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Abstract

Formation of synapses requires specific cellular interactions that organize pre- and postsynaptic compartments. The neuroligin-neurexin complex mediates heterophilic adhesion and can trigger assembly of glutamatergic and GABAergic synapses in cultured hippocampal neurons. Both neuroligins and neurexins are encoded by multiple genes. Alternative splicing generates large numbers of isoforms, which may engage in selective axo-dendritic interactions. We explored whether alternative splicing of the postsynaptic neuroligins modifies their activity toward glutamatergic and GABAergic axons. We find that small extracellular splice insertions restrict the function of neuroligin-1 and -2 to glutamatergic and GABAergic contacts and alter interaction with presynaptic neurexins. The neuroligin isoforms associated with GABAergic contacts bind to neurexin-1alpha and a subset of neurexin-1betas. In turn, these neurexin isoforms induce GABAergic but not glutamatergic postsynaptic differentiation. Our findings suggest that alternative splicing plays a central role in regulating selective extracellular interactions through the neuroligin-neurexin complex at glutamatergic and GABAergic synapses.

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Many known ASD genes, such as neuroligins and neurexins, display complex isoform-specific expression in brain, with different isoforms having distinct functions.
“Consistent with this notion, many known ASD genes, such as neuroligins and neurexins, display a complex pattern of isoform-specific expression in brain (Boucard et al., 2005; Sudhof, 2008), with different isoforms having very distinct functions (Chih et al., 2006).”
From Modeling Autism by SHANK Gene Mutations in Mice (2013) · cites this paper as Chih et al., 2006
NRXNβ AS4- isoforms preferentially bind neuroligin 1 at glutamatergic synapses, whereas NRXNβ AS4+ isoforms preferentially bind NLGN2 at GABAergic and glycinergic synapses.
“NRXNβ AS4– isoforms preferentially bind neurolignin 1 (B) concentrated at glutamatergic synapses, whereas NRXNβ AS4+ isoforms preferentially bind NLGN2(A) at GABAergic and glycin-ergic synapses93”
From The neurogenetics of alternative splicing (2016) · cites this paper as [93]

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Authors: Chih, B., Gollan, L., & Scheiffele, P.
Affiliations: Columbia University Irving Medical Center (US)
Corresponding author: Scheiffele, Peter
ORCID: Chih, Ben
Scheiffele, Peter
Venue: Neuron
Publisher: Elsevier BV
Published: 2006-07
Volume: 51
Issue: 2
Pages: 171-178
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2006.06.005
OpenAlex: W1992257474
Cited by: 393
References: 34
Citations by year: 2026: 13 · 2025: 22 · 2024: 10 · 2023: 13 · 2022: 17 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 16 · 2017: 18 · 2016: 20 · 2015: 29 · 2014: 18 · 2013: 28 · 2012: 20
FWCI: 9.56
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2573 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS045014)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: alternative splicing, neuroligins, neurexin, synaptogenesis, glutamatergic synapses, GABAergic synapses, neuroligin-1, neuroligin-2, postsynaptic differentiation, heterophilic adhesion
MeSH terms: Animals, Cells, Cultured, Chlorocebus aethiops, Glycoproteins, Hippocampus, Membrane Proteins, Nerve Tissue Proteins, Neurons, Neuropeptides, Synapses, Cell Adhesion Molecules, Neuronal, Alternative Splicing, COS Cells, Rats

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Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex

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