Complex formation of immunoglobulin superfamily molecules Side-IV and Beat-IIb regulates synaptic specificity

• Published in: Cell reports (Cambridge) 2024-02, Vol.43 (2), p.113798-113798, Article 113798
• Main Authors: Osaka, Jiro, Ishii, Arisa, Wang, Xu, Iwanaga, Riku, Kawamura, Hinata, Akino, Shogo, Sugie, Atsushi, Hakeda-Suzuki, Satoko, Suzuki, Takashi
• Format: Article
• Language: English
• Subjects: Beat and Side proteins; cell-surface proteins; CP: Immunology; CP: Neuroscience; Drosophila visual system; Dsyd-1-Liprin-α; irre cell recognition module; subcellular localization; synapse formation; synaptic specificity; transmembrane receptor clustering
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.113798

Neurons establish specific synapses based on the adhesive properties of cell-surface proteins while also retaining the ability to form synapses in a relatively non-selective manner. However, comprehensive understanding of the underlying mechanism reconciling these opposing characteristics remains incomplete. Here, we have identified Side-IV/Beat-IIb, members of the Drosophila immunoglobulin superfamily, as a combination of cell-surface recognition molecules inducing synapse formation. The Side-IV/Beat-IIb combination transduces bifurcated signaling with Side-IV’s co-receptor, Kirre, and a synaptic scaffold protein, Dsyd-1. Genetic experiments and subcellular protein localization analyses showed the Side-IV/Beat-IIb/Kirre/Dsyd-1 complex to have two essential functions. First, it narrows neuronal binding specificity through Side-IV/Beat-IIb extracellular interactions. Second, it recruits synapse formation factors, Kirre and Dsyd-1, to restrict synaptic loci and inhibit miswiring. This dual function explains how the combinations of cell-surface molecules enable the ranking of preferred interactions among neuronal pairs to achieve synaptic specificity in complex circuits in vivo. [Display omitted] •Side-IV binding to Beat-IIb regulates synaptic specificity in vivo•Side-IV/Beat-IIb forms complex with Kirre and Dsyd-1•Complex formation of Side-IV restricts synaptic locations and inhibits miswiring Osaka et al. demonstrate that Side-IV and Beat-IIb are cell-surface recognition molecules capable of inducing synapse by bifurcated signaling with co-receptor Kirre and scaffold protein Dsyd-1. The complex formation of Side-IV/Beat-IIb/Kirre/Dsyd-1 not only narrows the binding specificity but also restricts synaptic loci and inhibits miswiring.