It was recently reported that LPHN3-OLF also binds FLRT2 with low nM affinity and that neurons were repelled by the presence of LPHN3-OLF in the growth matrix of a stripe assay (Jackson et al., 2015). Moreover, overlay of the coordinates of the published mouse FLRT2-LRR in complex with the first Ig domain of UNC5D (PDB ID: 4V2C) (Seiradake et al., 2014) with our complex suggest that a trimeric complex composed by FLRT2 or FLRT3-LRR/LPHN 3-OLF/UNC5D-Ig1 is possible. Owing to this intricate recognition code between FLRTs and LPHN3, which may generate adhesion or repulsion, the structural characterization of the presented complex will be important to inform testable mechanistic-based hypotheses in the biology of synapse formation and in vivo axonal attraction and repulsion.
