Structural basis for teneurin function in circuit-wiring: a toxin motif at the synapse

• Autores: Jingxian Li, Moran Shalev-Benami, Richard Sando
• Localización: Cell, ISSN 0092-8674, Vol. 173, Nº. 3, 2018, págs. 735-748
• Idioma: inglés
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• Resumen

  • Teneurins (TENs) are cell-surface adhesion proteins with critical roles in tissue development and axon guidance. Here, we report the 3.1-Å cryoelectron microscopy structure of the human TEN2 extracellular region (ECR), revealing a striking similarity to bacterial Tc-toxins. The ECR includes a large β barrel that partially encapsulates a C-terminal domain, which emerges to the solvent through an opening in the mid-barrel region. An immunoglobulin (Ig)-like domain seals the bottom of the barrel while a β propeller is attached in a perpendicular orientation. We further show that an alternatively spliced region within the β propeller acts as a switch to regulate trans-cellular adhesion of TEN2 to latrophilin (LPHN), a transmembrane receptor known to mediate critical functions in the central nervous system. One splice variant activates trans-cellular signaling in a LPHN-dependent manner, whereas the other induces inhibitory postsynaptic differentiation. These results highlight the unusual structural organization of TENs giving rise to their multifarious functions.