FLRT Proteins Are Endogenous Latrophilin Ligands and Regulate Excitatory Synapse Development

Supplemental Information Postsynaptic FLRT Proteins Are Endogenous Ligands for the Black Widow Spider Venom Receptor Latrophilin and Regulate Excitatory Synapse Development

Structural Basis of Latrophilin-FLRT Interaction

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...

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion.

Fibronectin 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 ...

FLRT Structure: Balancing Repulsion and Cell Adhesion in Cortical and Vascular Development

FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion ...

Unbiased Discovery of Glypican as a Receptor for LRRTM4 in Regulating Excitatory Synapse Development

Leucine-rich repeat (LRR) proteins have recently been identified as important regulators of synapse development and function, but for many LRR proteins the ligand-receptor interactions are not known. Here we identify the heparan sulfate (HS) proteoglycan glypican as a receptor for LRRTM4 using an unbiased proteomics-based approach. Glypican binds LRRTM4, but not LRRTM2, in an HS-dependent manne...