Title : Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion
Abstract :
- Fibronectin leucine-rich repeat transmembrane proteins leucine-rich repeat transmembrane proteins ( FLRTs ) are cell-adhesion molecules with emerging functions in cortical development and synapse formation
- Their extracellular regions interact with latrophilins (LPHNs) to mediate synapse development, and with Uncoordinated-5 (UNC5)/netrin receptors to control the migration of neurons in the developing cortex
- Here, we present the crystal structures of FLRT3 in isolation and in complex with LPHN3
- The L LPHN3 / FLRT3 structure reveals that LPHN3 binds to FLRT3 at a site distinct from UNC5
- Structure-based mutations specifically disrupt LPHN3 L PHN3/ FLRT3 binding, but do not disturb their interactions with other proteins or their cell-membrane localization
- Thus, they can be used as molecular tools to dissect the functions of FLRTs and LPHNs in vivo
- Our results suggest that UNC5 and LPHN3 can simultaneously bind to FLRT3 , forming a trimeric complex, and that FLRT3 may form transsynaptic complexes with both LPHN3 and UNC5
- These findings provide molecular insights for understanding the role of cell-adhesion proteins in synapse function