[PDF][PDF] Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins

D Schreiner, TM Nguyen, G Russo, S Heber… - Neuron, 2014 - cell.com
D Schreiner, TM Nguyen, G Russo, S Heber, A Patrignani, E Ahrné, P Scheiffele
Neuron, 2014cell.com
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 …
Summary
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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