National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01-GM120322
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01 DK090165
米国
引用
ジャーナル: Cell / 年: 2018 タイトル: Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse. 著者: Jingxian Li / Moran Shalev-Benami / Richard Sando / Xian Jiang / Amanuel Kibrom / Jie Wang / Katherine Leon / Christopher Katanski / Olha Nazarko / Yue C Lu / Thomas C Südhof / Georgios ...著者: Jingxian Li / Moran Shalev-Benami / Richard Sando / Xian Jiang / Amanuel Kibrom / Jie Wang / Katherine Leon / Christopher Katanski / Olha Nazarko / Yue C Lu / Thomas C Südhof / Georgios Skiniotis / Demet Araç / 要旨: 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 ...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 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.