Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins

Davide Comoletti, Robyn E. Flynn, Antony A. Boucard, Borries Demeler, Virgil Schirf, Jianxin Shi, Lori L. Jennings, Helen R. Newlin, Thomas C. Südhof, Palmer Taylor

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating presynaptic maturation via interactions with β3-neurexin. Both neuroligins and β-neurexins have alternatively spliced inserts in their extracellular domains. Using analytical ultracentrifugation, we determined that the extracellular domains of the neuroligins sediment as dimers, whereas the extracellular domains of the β-neurexins appear monomeric. Sedimentation velocity experiments of titrated stoichiometry ratios of β-neurexin and neuroligin suggested a 2:2 complex formation. The recognition properties of individual neuroligins toward β-neurexin-1 (NX1β), along with the influence of their splice inserts, were explored by surface plasmon resonance and affinity chromatography. Different neuroligins display a range of NX1β affinities spanning more than 2 orders of magnitude. Whereas splice insert 4 in β-neurexin appears to act only as a modulator of the neuroligin/β- neurexin association, splice insert B in neuroligin-1 (NL1) is the key element regulating the NL1/NX1β binding. Our data indicate that gene selection, mRNA splicing, and post-translational modifications combine to give rise to a controlled neuroligin recognition code with a rank ordering of affinities for particular neurexins that is conserved for the neuroligins across mammalian species.

Original languageEnglish (US)
Pages (from-to)12816-12827
Number of pages12
JournalBiochemistry
Volume45
Issue number42
DOIs
StatePublished - Oct 24 2006

ASJC Scopus subject areas

  • Biochemistry

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