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Neuron. 2014 Oct 22;84(2):386-98. doi: 10.1016/j.neuron.2014.09.011. Epub 2014 Oct 2.

Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.

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Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Winterthurerstrasse 190/Y32 H66, 8057 Zurich, Switzerland.
Department of Computer Science & Bioinformatics Research Center, North Carolina State University, Campus Box 7566, Raleigh, NC 27695, USA.
Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland. Electronic address:


Molecular diversity of surface receptors has been hypothesized to provide a mechanism for selective synaptic connectivity. Neurexins are highly diversified receptors that drive the morphological and functional differentiation of synapses. Using a single cDNA sequencing approach, we detected 1,364 unique neurexin-α and 37 neurexin-β mRNAs produced by alternative splicing of neurexin pre-mRNAs. This molecular diversity results from near-exhaustive combinatorial use of alternative splice insertions in Nrxn1α and Nrxn2α. By contrast, Nrxn3α exhibits several highly stereotyped exon selections that incorporate novel elements for posttranscriptional regulation of a subset of transcripts. Complexity of Nrxn1α repertoires correlates with the cellular complexity of neuronal tissues, and a specific subset of isoforms is enriched in a purified cell type. Our analysis defines the molecular diversity of a critical synaptic receptor and provides evidence that neurexin diversity is linked to cellular diversity in the nervous system.

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