Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism

Jingxian Li, Yuan Xie, Shaleeka Cornelius, Xian Jiang, Richard Sando, Szymon P. Kordon, Man Pan, Katherine Leon, Thomas C. Südhof, Minglei Zhao () and Demet Araç ()
Additional contact information
Jingxian Li: The University of Chicago
Yuan Xie: The University of Chicago
Shaleeka Cornelius: Stanford University
Xian Jiang: Stanford University
Richard Sando: Stanford University
Szymon P. Kordon: The University of Chicago
Man Pan: The University of Chicago
Katherine Leon: The University of Chicago
Thomas C. Südhof: Stanford University
Minglei Zhao: The University of Chicago
Demet Araç: The University of Chicago

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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. 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16029-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16029-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16029-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().