Neurexin mediates the assembly of presynaptic terminals
Open accessAbstract
Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.
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Neurexins are presynaptic adhesion molecules critical for synaptic transmission.
“Neurexins, presynaptic adhesion molecules, are critical for synaptic transmission. 55”
From Deletion of neuronal <i>Idol</i> ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [55]
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“55 58 Increased neurexin signaling may contribute to the enrichment of biological processes and networks such as “synapse organization,” “cell adhesion_synaptic contact,” and “cell adhesion_amyloid proteins” in 5XFAD;Neu cKO mice (Figure 7F,G).”
- Authors
- Dean, C., Scholl, F. G., Choih, J., DeMaria, S., Berger, J., Isacoff, E., & Scheiffele, P.
- Affiliations
- University of California, Berkeley (US)
- Columbia University (US)
- Corresponding author
- Scheiffele, Peter
- Venue
- Nature Neuroscience
- Published
- 2003-06-08
- Volume
- 6
- Issue
- 7
- Pages
- 708-716
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC1646425
- OpenAlex
- W2130421403
- Cited by
- 617
- References
- 1
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 24 · 2023: 16 · 2022: 18 · 2021: 25 · 2020: 8 · 2019: 20 · 2018: 22 · 2017: 26 · 2016: 23 · 2015: 31 · 2014: 24 · 2013: 32 · 2012: 37
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH60771, R01MH060711)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- neurexin, neuroligin-1, presynaptic differentiation, synaptogenesis, exocytosis, cytoplasmic domain, postsynaptic receptors
- MeSH terms
- Alanine, Animals, Animals, Newborn, Binding Sites, Calcium-Binding Proteins, Cell Aggregation, Cell Communication, Cell Differentiation, Cells, Cultured, Cerebellum, Chickens, Choline O-Acetyltransferase, Female, Hippocampus, Humans, Kidney, Lipid Bilayers, Membrane Glycoproteins, Membrane Proteins, Mutation, Nerve Tissue Proteins, Pons, Recombinant Proteins, RNA-Dependent RNA Polymerase, Structure-Activity Relationship, Synapses, Synaptic Vesicles, Time Factors, Transfection, Viral Proteins, Blotting, Western, Cell Adhesion Molecules, Neuronal, Proto-Oncogene Proteins c-myc, PC12 Cells, Presynaptic Terminals, Receptors, AMPA, Immunomagnetic Separation, Structural Homology, Protein, R-SNARE Proteins, Synaptotagmins, Mice, Rats
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