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Journal Article

Structural basis of Teneurin-Latrophilin interaction in repulsive guidance of migrating neurons

MPS-Authors
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del Toro,  Daniel
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Ruff,  Tobias
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Seyit-Bremer,  Goenuel
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Brignani,  Sara
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Klein,  Rüdiger
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Fulltext (public)

1-s2.0-S0092867419313765-main.pdf
(Publisher version), 14MB

Supplementary Material (public)

1-s2.0-S0092867419313765-mmc1.pdf
(Supplementary material), 144KB

Citation

del Toro, D., Carrasquero-Ordaz, M. A., Chu, A., Ruff, T., Shahin, M., Jackson, V. A., et al. (2020). Structural basis of Teneurin-Latrophilin interaction in repulsive guidance of migrating neurons. Cell, 180(2), 323-339.e19. doi:10.1016/j.cell.2019.12.014.


Cite as: https://hdl.handle.net/21.11116/0000-0005-BD8A-B
Abstract
Teneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins are also expressed during murine cortical cell migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes that reveal how the lectin and olfactomedin domains of Latrophilin bind across a spiraling beta-barrel domain of Teneurin, the YD shell. We couple structure-based protein engineering to biophysical analysis, cell migration assays, and in utero electroporation experiments to probe the importance of the interaction in cortical neuron migration. We show that binding of Latrophilins to Teneurins and FLRTs directs the migration of neurons using a contact repulsion-dependent mechanism. The effect is observed with cell bodies and small neurites rather than their processes. The results exemplify how a structure-encoded synaptogenic protein complex is also used for repulsive cell guidance.