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Structural basis for teneurin function in circuit‐wiring: A toxin motif at the synapse
Author(s) -
Arac Demet
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.779.1
Subject(s) - microbiology and biotechnology , transmembrane protein , transmembrane domain , axon , structural motif , biology , receptor , chemistry , genetics , biochemistry
Teneurins (TENs) are cell‐surface adhesion proteins with critical roles in tissue development and axon guidance. Here we report the 3.1‐Å electron cryo‐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. Support or Funding Information NIGMS This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .