Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons - Archive ouverte HAL Access content directly
Journal Articles Cell Year : 2020

Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons

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1
Daniel del Toro
  • Function : Author
Maria A. Carrasquero-Ordaz
  • Function : Author
Amy Chu
  • Function : Author
Tobias Ruff
  • Function : Author
Meriam Shahin
  • Function : Author
Verity A. Jackson
  • Function : Author
Miguel Berbeira-Santana
  • Function : Author
Goenuel Seyit-Bremer
  • Function : Author
Sara Brignani
  • Function : Author
Rainer Kaufmann
  • Function : Author
Edward Lowe
  • Function : Author
Rüdiger Klein
  • Function : Author
Elena Seiradake
  • Function : Author

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.

Dates and versions

hal-03019038 , version 1 (23-11-2020)

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Daniel del Toro, Maria A. Carrasquero-Ordaz, Amy Chu, Tobias Ruff, Meriam Shahin, et al.. Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons. Cell, 2020, 180 (2), pp.323-339.e19. ⟨10.1016/j.cell.2019.12.014⟩. ⟨hal-03019038⟩
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