title: Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.
abstract: 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.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schreiner
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Thi-Minh
authors.initials: TM
authors.lastname: Nguyen
authors.affiliation: Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Winterthurerstrasse 190/Y32 H66, 8057 Zurich, Switzerland.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Computer Science & Bioinformatics Research Center, North Carolina State University, Campus Box 7566, Raleigh, NC 27695, USA.
authors.forename: Steffen
authors.initials: S
authors.lastname: Heber
authors.affiliation: Functional Genomics Center Zurich, ETH Zurich/University of Zurich, Winterthurerstrasse 190/Y32 H66, 8057 Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Patrignani
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland.
authors.forename: Erik
authors.initials: E
authors.lastname: Ahrné
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, 4056 Basel, Switzerland. Electronic address: peter.scheiffele@unibas.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger