Cited by 810Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeuroinflammation and Neurodegeneration Mechanisms

Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits

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Südhof, Thomas C.·2017·Cell

Abstract

Synapses are specialized junctions between neurons in brain that transmit and compute information, thereby connecting neurons into millions of overlapping and interdigitated neural circuits. Here, we posit that the establishment, properties, and dynamics of synapses are governed by a molecular logic that is controlled by diverse trans-synaptic signaling molecules. Neurexins, expressed in thousands of alternatively spliced isoforms, are central components of this dynamic code. Presynaptic neurexins regulate synapse properties via differential binding to multifarious postsynaptic ligands, such as neuroligins, cerebellin/GluD complexes, and latrophilins, thereby shaping the input/output relations of their resident neural circuits. Mutations in genes encoding neurexins and their ligands are associated with diverse neuropsychiatric disorders, especially schizophrenia, autism, and Tourette syndrome. Thus, neurexins nucleate an overall trans-synaptic signaling network that controls synapse properties, which thereby determines the precise responses of synapses to spike patterns in a neuron and circuit and which is vulnerable to impairments in neuropsychiatric disorders.

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Authors
Südhof, T. C.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Südhof, Thomas C.
Venue
Cell
Publisher
Elsevier BV
Published
2017-11
Volume
171
Issue
4
Pages
745-769
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2765792294
Cited by
810
References
230
Citations by year
2026: 102 · 2025: 76 · 2024: 92 · 2023: 103 · 2022: 82 · 2021: 109 · 2020: 97 · 2019: 85 · 2018: 61 · 2017: 1
FWCI
8.26
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIMH (MH052804, MH086403, MH092931)
  • NINDS (NS094733)
  • NIA (AG04813101)
  • HHMI
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
neurexin, trans-synaptic signaling, neuroligins, latrophilin, synaptic plasticity, neural circuits, alternative splicing, neuropsychiatric disorders, schizophrenia, autism spectrum disorder, Tourette syndrome
MeSH terms
Animals, Autistic Disorder, Tourette Syndrome, Humans, Membrane Glycoproteins, Neural Pathways, Schizophrenia, Synapses, Signal Transduction, Cell Adhesion Molecules, Neuronal, Alternative Splicing, Protein Isoforms

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