Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

Structural basis of latrophilin-FLRT interaction


del Toro,  Daniel
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;


Klein,  Rüdiger
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
Supplementary Material (public)
There is no public supplementary material available

Jackson, V. A., del Toro, D., Carrasquero, M., Roversi, P., Harlos, K., Klein, R., et al. (2015). Structural basis of latrophilin-FLRT interaction. Structure, 23(4), 774-781. doi:10.1016/j.str.2015.01.013.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0026-C993-9
Latrophilins, receptors for spider venom alpha-latrotoxin, are adhesion type G-protein-coupled receptors with emerging functions in synapse development. The N-terminal region binds the endogenous cell adhesion molecule FLRT, a major regulator of cortical and synapse development. We present crystallographic data for the mouse Latrophilin3 lectin and olfactomedin-like (Olf) domains, thereby revealing the Olf beta-propeller fold and conserved calcium-binding site. We locate the FLRT-Latrophilin binding surfaces by a combination of sequence conservation analysis, point mutagenesis, and surface plasmon resonance experiments. In stripe assays, we show that wild-type Latrophilin3 and its high-affinity interactor FLRT2, but not the binding-impaired mutants we generated, promote HeLa cell adhesion. In contrast, cortical neurons expressing endogenous FLRTs are repelled by wild-type Latrophilin3 and not by the binding-impaired mutant. Taken together, we present molecular level insights into Latrophilin structure, its FLRT-binding mechanism, and a role for Latrophilin and FLRT that goes beyond a simply adhesive interaction.