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-Structure paper
Title | Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 2140, Year 2020 |
Publish date | May 1, 2020 |
![]() | Jingxian Li / Yuan Xie / Shaleeka Cornelius / Xian Jiang / Richard Sando / Szymon P Kordon / Man Pan / Katherine Leon / Thomas C Südhof / Minglei Zhao / Demet Araç / ![]() |
PubMed Abstract | The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. ...The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) 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 alternative-splicing regulates TEN-LPHN interaction remains unclear. Here, we report the 2.9 Å 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 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. |
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Methods | EM (single particle) |
Resolution | 2.97 Å |
Structure data | EMDB-21205, PDB-6vhh: |
Chemicals | ![]() ChemComp-NAG: |
Source |
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![]() | MEMBRANE PROTEIN / Adhesion GPCR / synapse / Teneurin / Lphn |