Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions

Xiaoyan Chen, Heli Liu, Ann H.R. Shim, Pamela J. Focia, Xiaolin He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 Å between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1β (NX1β) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1β interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalNature Structural and Molecular Biology
Volume15
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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