PMID: 18084303

 

    Legend: Sugar

Title : Structural basis for synaptic adhesion mediated by neuroligin- neurexin interactions

Abstract :

1. The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses
2. The neuroligin- neurexin adhesion is Ca2 +-dependent and regulated by alternative splicing
3. We report a structure of the complex at a resolution of 2.4 A between the mouse neuroligin-1 ( NL1 ) cholinesterase-like domain and the mouse neurexin-1beta ( NX1beta ) LNS ( laminin , neurexin and sex hormone-binding globulin-like) domain
4. 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
5. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1- NX1beta interface
6. 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