ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
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Who cites it
204 citing papers in PubMed.
- Towards modelling mental disorders in zebrafish. Neurexins severely modulate anxiety, affiliative social behaviour and aggression.Molecular psychiatry · 2026Article
- Alternative splicing plasticity of the neurexin family of synaptic adhesion molecules in human sensory neurons.bioRxiv : the preprint server for biology · 2026Article
- In vivo dissection of human NRXN1 isoforms reveals gain-of-function pathogenicity of schizophrenia-associated 3' deletions.Human molecular genetics · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Synaptic Ca2+ channels and neurexins are linked through direct and indirect binding complexes.Scientific reports · 2026Article
- MASQ: A multiplex qPCR platform for quantitative alternative splicing analysis in clinical specimens.Molecular therapy. Nucleic acids · 2026Article
- Molecular continuity between axon guidance and synaptic function.Molecules and cells · 2026Review
- Roles of synaptic cell adhesion molecules in the neuromodulatory systems.Molecules and cells · 2026Review
- Cerebellar hypoplasia caused by calcium/calmodulin-dependent serine protein kinase deficiency.Molecules and cells · 2026Review
- Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases.Communications biology · 2026Review
- Ethanol Alters the Neurexin Landscape in Human Neuroblastoma Cells.Alcohol, clinical & experimental research · 2026Article
- RNA isoform diversity, splicing variants and switching in single cells of the Alzheimer's disease brain.Communications biology · 2026Article
- Decoding exon inclusion in the human brain reveals more divergent splicing mechanisms in neurons than glia.Genome biology · 2026Article
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- Roles of NRXN1 in neuropsychiatric disorders: from genetic lesion to molecular mechanism.Frontiers in neuroscience · 2026Review
- Cell-type-resolvedbioRxiv : the preprint server for biology · 2025Article
- REST elevation-dependent chromatin remodeling and alternative Grk6 transcript synthesis hyperactivates Cxcr4-Sdf1 signaling in cerebellar granule cell progenitors.bioRxiv : the preprint server for biology · 2025Article
- Membrane trafficking of synaptic adhesion molecules.The Journal of physiology · 2025Review
- The Glycosaminoglycan-Dependent Interactome of Neurexin-1 in Human Fetal Glial Cells.Proteoglycan research · 2025Article
- RNA isoform diversity, splicing variants, and switching in single cells of the Alzheimer's disease brain.Research square · 2025Article
144 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Neurexins are evolutionarily conserved presynaptic cell-adhesion molecules that are essential for normal synapse formation and synaptic transmission. Indirect evidence has indicated that extensive alternative splicing of neurexin mRNAs may produce hundreds if not thousands of neurexin isoforms, but no direct evidence for such diversity has been available. Here we use unbiased long-read sequencing of full-length neurexin (Nrxn)1α, Nrxn1β, Nrxn2β, Nrxn3α, and Nrxn3β mRNAs to systematically assess how many sites of alternative splicing are used in neurexins with a significant frequency, and whether alternative splicing events at these sites are independent of each other. In sequencing more than 25,000 full-length mRNAs, we identified a novel, abundantly used alternatively spliced exon of Nrxn1α and Nrxn3α (referred to as alternatively spliced sequence 6) that encodes a 9-residue insertion in the flexible hinge region between the fifth LNS (laminin-α, neurexin, sex hormone-binding globulin) domain and the third EGF-like sequence. In addition, we observed several larger-scale events of alternative splicing that deleted multiple domains and were much less frequent than the canonical six sites of alternative splicing in neurexins. All of the six canonical events of alternative splicing appear to be independent of each other, suggesting that neurexins may exhibit an even larger isoform diversity than previously envisioned and comprise thousands of variants. Our data are consistent with the notion that α-neurexins represent extracellular protein-interaction scaffolds in which different LNS and EGF domains mediate distinct interactions that affect diverse functions and are independently regulated by independent events of alternative splicing.
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