Rxivist logo

Structure of the teneurin-latrophilin complex: Alternative splicing controls synapse specificity by a novel mechanism

By Jingxian Li, Yuan Xie, Shaleeka Cornelius, Xian Jiang, Szymon P Kordon, Richard Sando, Man Pan, Katherine Leon, Thomas C. Südhof, Minglei Zhao, Demet Araç

Posted 14 Jan 2020
bioRxiv DOI: 10.1101/2020.01.13.901090

The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. Insertion of a short alternatively-spliced region within TENs abolishes the TEN-LPHN interaction and switches TEN function to specify inhibitory synapses. How TENs bind to LPHNs in a manner regulated by alternative splicing remains unclear. Here, we report the high-resolution cryo-EM structure of the TEN2-LPHN3 complex, and describe the trimeric TEN2-LPHN3-FLRT3 complex. The structure reveals that the N-terminal lectin-like domain of LPHN3 binds to the TEN2 barrel at a site far away from the alternatively-spliced region. Alternative-splicing regulates the TEN2-LPHN3 interaction by hindering access to the LPHN-binding surface rather than altering it. Strikingly, mutagenesis of the LPHN-binding surface of TEN2 abolishes the LPHN3 interaction and impairs excitatory but not inhibitory synapse formation. These results suggest that a multi-level coincident binding mechanism mediated by a cryptic adhesion complex between TENs and LPHNs regulates synapse specificity.

Download data

  • Downloaded 585 times
  • Download rankings, all-time:
    • Site-wide: 38,800
    • In biochemistry: 966
  • Year to date:
    • Site-wide: 54,577
  • Since beginning of last month:
    • Site-wide: 66,209

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News