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Structural basis of teneurin-latrophilin interaction in repulsive guidance of migrating neurons

DOI: 10.1016/j.cell.2019.12.014 DOI Help

Authors: Daniel Del Toro (Max Planck Institute of Neurobiology; University of Barcelona) , Maria A. Carrasquero-ordaz (Oxford University) , Amy Chu (Oxford University) , Tobias Ruff (Max Planck Institute of Neurobiology) , Meriam Shahin (Oxford University) , Verity A. Jackson (University of Oxford) , Matthieu Chavent (IPBS) , Miguel Berbeira-santana (Oxford University) , Goenuel Seyit-bremer (Max Planck Institute of Neurobiology) , Sara Brignani (Max Planck Institute of Neurobiology) , Rainer Kaufmann (University of Hamburg) , Edward Lowe (Oxford University) , RĂ¼diger Klein (Max Planck Institute of Neurobiology) , Elena Seiradake (Oxford University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 12346 , 1838

Open Access Open Access

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.

Journal Keywords: Teneurin; Latrophilin; FLRT; adhesion; repulsion; neuronal migration; cortex development; radial glia; pyramidal neuron

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography