Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse.
Cell
; 173(3): 735-748.e15, 2018 04 19.
Article
in En
| MEDLINE
| ID: mdl-29677516
ABSTRACT
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 ß 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 ß propeller is attached in a perpendicular orientation. We further show that an alternatively spliced region within the ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
/
Bacterial Toxins
/
Membrane Proteins
/
Nerve Tissue Proteins
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell
Year:
2018
Document type:
Article
Affiliation country:
Estados Unidos