Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse.

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. Copyright © 2018 Elsevier Inc. All rights reserved.

Citation

Jingxian Li, Moran Shalev-Benami, Richard Sando, Xian Jiang, Amanuel Kibrom, Jie Wang, Katherine Leon, Christopher Katanski, Olha Nazarko, Yue C Lu, Thomas C Südhof, Georgios Skiniotis, Demet Araç. Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse. Cell. 2018 Apr 19;173(3):735-748.e15

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PMID: 29677516

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