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

Abstract:

:Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating presynaptic maturation via interactions with beta-neurexin. Both neuroligins and beta-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 beta-neurexins appear monomeric. Sedimentation velocity experiments of titrated stoichiometry ratios of beta-neurexin and neuroligin suggested a 2:2 complex formation. The recognition properties of individual neuroligins toward beta-neurexin-1 (NX1beta), along with the influence of their splice inserts, were explored by surface plasmon resonance and affinity chromatography. Different neuroligins display a range of NX1beta affinities spanning more than 2 orders of magnitude. Whereas splice insert 4 in beta-neurexin appears to act only as a modulator of the neuroligin/beta-neurexin association, splice insert B in neuroligin-1 (NL1) is the key element regulating the NL1/NX1beta 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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Comoletti D,Flynn RE,Boucard AA,Demeler B,Schirf V,Shi J,Jennings LL,Newlin HR,Südhof TC,Taylor P

doi

10.1021/bi0614131

subject

Has Abstract

pub_date

2006-10-24 00:00:00

pages

12816-27

issue

42

eissn

0006-2960

issn

1520-4995

journal_volume

45

pub_type

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