# A trans-synaptic IgLON adhesion molecular complex directly contacts and clusters a nicotinic receptor

## TL;DR

This study shows how a specific protein complex helps organize nerve cell communication by directly interacting with a receptor involved in signal transmission.

## Contribution

The discovery that IgLON adhesion molecules directly cluster nicotinic receptors through extracellular interactions is novel.

## Key findings

- RIG-5 and ZIG-8 form a trans-synaptic complex that interacts via their Ig domains.
- ZIG-8 directly binds to the nicotinic receptor ACR-16 through a cis-interaction.
- IgLON interactions may organize synapses and directly interact with ionotropic receptors in mammals.

## Abstract

The clustering of neurotransmitter receptors at appropriate postsynaptic sites is essential for controlling synaptic transmission. While most known mechanisms involve receptor binding with cytoplasmic scaffolds, recent evidence highlights the importance of extracellular interactions that directly target receptors. Using Caenorhabditis elegans, we identified a trans-synaptic complex that involves RIG-5 and ZIG-8, two adhesion molecules of the immunoglobulin (Ig) superfamily and orthologous to Drosophila DIPs and Dprs, and mammalian IgLONs. Our results show that RIG-5 and ZIG-8 are anchored in the pre- and postsynaptic membranes, respectively, and interact in vivo via their first Ig domains. Furthermore, ZIG-8 directly binds a α7-like acetylcholine receptor (AChR), known as ACR-16, via a cis-interaction between its Ig2 domain and the base of the extracellular AChR domain. This study provides direct evidence that trans-synaptic IgLON interactions can organize neurochemical synapses and suggests that the IgLONs may directly interact with ionotropic receptors in the mammalian nervous system.

Synaptic extracellular proteins increasingly emerge as key organizers of neurotransmitter receptors. Here, authors show that an IgLON family cell adhesion molecule directly traps a nicotinic receptor through extracellular interactions.