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Article Dans Une Revue Cell Année : 2020

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

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

Résumé

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 et versions

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

Identifiants

Citer

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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