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Structure and Evolution of Neurexin Genes: Insight into the Mechanism of Alternative Splicing
Abstract
Neurexins are neuron-specific vertebrate proteins with hundreds of differentially spliced isoforms that may function in synapse organization. We now show that Drosophila melanogaster and Caenorhabditis elegans express a single gene encoding only an alpha-neurexin, whereas humans and mice express three genes, each of which encodes alpha- and beta-neurexins transcribed from separate promoters. The neurexin genes are very large (up to 1.62 Mb), with the neurexin-3 gene occupying almost 2% of human chromosome 14. Although invertebrate and vertebrate neurexins exhibit a high degree of evolutionary conservation, only vertebrate neurexins are subject to extensive alternative splicing that uses mechanisms ranging from strings of mini-exons to multiple alternative splice donor and acceptor sites. Consistent with their proposed role in synapse specification, neurexins thus have evolved from relatively simple genes in invertebrates to diversified genes in vertebrates with multiple promoters and extensive alternative splicing.
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“Pre-mRNAs from the three Nrxn genes undergo extensive alternative splicing to produce more than 3,000 protein isoforms88,89”
From The neurogenetics of alternative splicing (2016) · cites this paper as [89]
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Research works printed but not linked: 1
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Neuroligins and neurexins link synaptic function to cognitive disease
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Self-citationNeurexins Induce Differentiation of GABA and Glutamate Postsynaptic Specializations via Neuroligins
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Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits
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α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis
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Metadata
- Authors
- Tabuchi, K., & Südhof, T. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 79
- Issue
- 6
- Pages
- 849-859
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W2051468191
- Cited by
- 305
- References
- 31
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 9 · 2023: 13 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 10 · 2016: 12 · 2015: 15 · 2014: 19 · 2013: 16 · 2012: 17
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01 MH52804, R01MH052804)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- neurexin, alternative splicing, gene evolution, NRXN3, multiple promoters, mini-exon, alternative splice sites, Drosophila melanogaster, Caenorhabditis elegans, chromosome 14, gene structure
- MeSH terms
- Animals, Humans, Nerve Tissue Proteins, Alternative Splicing, Sequence Analysis, DNA, Evolution, Molecular, Mice
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