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 journalArticle

95 Citations (Scopus)

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

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Alternative Splicing
Genes
Affinity chromatography
Surface Plasmon Resonance
Ultracentrifugation
Surface plasmon resonance
Post Translational Protein Processing
Processing
Affinity Chromatography
Sedimentation
Stoichiometry
Dimers
Modulators
Sediments
Association reactions
Messenger RNA
Proteins
Experiments
neuroligin 1

ASJC Scopus subject areas

  • Biochemistry

Cite this

Comoletti, D., Flynn, R. E., Boucard, A. A., Demeler, B., Schirf, V., Shi, J., ... Taylor, P. (2006). Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins. Biochemistry, 45(42), 12816-12827. https://doi.org/10.1021/bi0614131

Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins. / Comoletti, Davide; Flynn, Robyn E.; Boucard, Antony A.; Demeler, Borries; Schirf, Virgil; Shi, Jianxin; Jennings, Lori L.; Newlin, Helen R.; Südhof, Thomas C.; Taylor, Palmer.

In: Biochemistry, Vol. 45, No. 42, 24.10.2006, p. 12816-12827.

Research output: Contribution to journalArticle

Comoletti, D, Flynn, RE, Boucard, AA, Demeler, B, Schirf, V, Shi, J, Jennings, LL, Newlin, HR, Südhof, TC & Taylor, P 2006, 'Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins', Biochemistry, vol. 45, no. 42, pp. 12816-12827. https://doi.org/10.1021/bi0614131
Comoletti, Davide ; Flynn, Robyn E. ; Boucard, Antony A. ; Demeler, Borries ; Schirf, Virgil ; Shi, Jianxin ; Jennings, Lori L. ; Newlin, Helen R. ; Südhof, Thomas C. ; Taylor, Palmer. / Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for β-neurexins. In: Biochemistry. 2006 ; Vol. 45, No. 42. pp. 12816-12827.
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