September 22, 2019  |  

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

Authors: Schreiner, Dietmar and Nguyen, Thi-Minh and Russo, Giancarlo and Heber, Steffen and Patrignani, Andrea and Ahrné, Erik and Scheiffele, Peter

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-a and 37 neurexin-ß mRNAs produced by alternative splicing of neurexin pre-mRNAs. This molecular diversity results from near-exhaustive combinatorial use of alternative splice insertions in Nrxn1a and Nrxn2a. By contrast, Nrxn3a exhibits several highly stereotyped exon selections that incorporate novel elements for posttranscriptional regulation of a subset of transcripts. Complexity of Nrxn1a 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. Copyright © 2014 Elsevier Inc. All rights reserved.

Journal: Neuron
DOI: 10.1016/j.neuron.2014.09.011
Year: 2014

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