Splice form dependence of beta-neurexin/neuroligin binding interactions.

Neuron
Jesko KoehnkeXiangshu Jin

Abstract

Alternatively spliced beta-neurexins (beta-NRXs) and neuroligins (NLs) are thought to have distinct extracellular binding affinities, potentially providing a beta-NRX/NL synaptic recognition code. We utilized surface plasmon resonance to measure binding affinities between all combinations of alternatively spliced beta-NRX 1-3 and NL 1-3 ectodomains. Binding was observed for all beta-NRX/NL pairs. The presence of the NL1 B splice insertion lowers beta-NRX binding affinity by approximately 2-fold, while beta-NRX splice insertion 4 has small effects that do not synergize with NL splicing. New structures of glycosylated beta-NRXs 1 and 2 containing splice insertion 4 reveal that the insertion forms a new beta strand that replaces the beta10 strand, leaving the NL binding site intact. This helps to explain the limited effect of splice insert 4 on NRX/NL binding affinities. These results provide new structural insights and quantitative binding information to help determine whether and how splice isoform choice plays a role in beta-NRX/NL-mediated synaptic recognition.

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