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.

  1. School of Life Science and Technology, Tokyo Institute of Technology
  2. Brain Research Institute, Niigata University
  3. Research Initiatives and Promotion Organization, Yokohama National University


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.

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