Structural basis of Latrophilin-FLRT interaction

Journal article

Latrophilins, receptors for spider venom α-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 β-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.

Authors: Jackson, V; del Toro, D; Ordaz, M; Roversi, P; Harlos, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Structure
• Volume: 23
• Issue: 4
• Pages: 774-781
• Publication date: 2015-02-26
• Acceptance date: 2015-01-19
• DOI: 10.1016/j.str.2015.01.013
• EISSN: 1878-4186
• ISSN: 0969-2126
• Language: English