2024.04.05
Complex formation of immunoglobulin superfamily molecules Side-IV and Beat-IIb regulates synaptic specificity
▶ Cell Rep. 2024 Feb 27;43(2):113798. doi: 10.1016/j.celrep.2024.113798. Epub 2024 Feb 20.
Osaka J1,2, Ishii A1, Wang X1, Iwanaga R1, Kawamura H1, Akino S1, Sugie A2, Hakeda-Suzuki S1,3, Suzuki T1.
Abstract
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.
*Reprinted under a CC BY NC ND 4.0 license.