Higher-Order Architecture of Cell Adhesion Mediated by Polymorphic Synaptic Adhesion Molecules Neurexin and Neuroligin

SummaryPolymorphic adhesion molecules neurexin and neuroligin (NL) mediate asymmetric trans-synaptic adhesion, which is crucial for synapse development and function. It is not known whether or how individual synapse function is controlled by the interactions between variants and isoforms of these molecules with differing ectodomain regions. At a physiological concentration of Ca2+, the ectodomain complex of neurexin-1 β isoform (Nrx1β) and NL1 spontaneously assembled into crystals of a lateral sheet-like superstructure topologically compatible with transcellular adhesion. Correlative light-electron microscopy confirmed extracellular sheet formation at the junctions between Nrx1β- and NL1-expressing non-neuronal cells, mimicking the close, parallel synaptic membrane apposition. The same NL1-expressing cells, however, did not form this higher-order architecture with cells expressing the much longer neurexin-1 α isoform, suggesting a functional discrimination mechanism between synaptic contacts made by different isoforms of neurexin variants.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Nrx1β/NL1 ectodomain complexes formed a layer in an unusual Ca2+-induced crystal
► Similar layer was visualized on cells by correlative light-electron microscopy
► Such a layer was not formed when Nrx1α-expressing cells were used
► Receptor ectodomain polymorphism leads to a unique synaptic adhesion structure