Latrophilin GPCRs direct synapse specificity by coincident binding of FLRTs and teneurins

Science
Richard SandoThomas C Südhof

Abstract

Bidirectional signaling by cell adhesion molecules is thought to mediate synapse formation, but the mechanisms involved remain elusive. We found that the adhesion G protein-coupled receptors latrophilin-2 and latrophilin-3 selectively direct formation of perforant-path and Schaffer-collateral synapses, respectively, to hippocampal CA1-region neurons. Latrophilin-3 binds to two transcellular ligands: fibronectin leucine-rich repeat transmembrane proteins (FLRTs) and teneurins. In transgenic mice in vivo, both binding activities were required for input-specific synapse formation, which suggests that coincident binding of both ligands is necessary for synapse formation. In cultured neurons in vitro, teneurin or FLRT alone did not induce excitatory synapse formation, whereas together they potently did so. Thus, postsynaptic latrophilins promote excitatory synapse formation by simultaneous binding of two unrelated presynaptic ligands, which is required for formation of synaptic inputs at specific dendritic localizations.

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Citations

Jul 25, 2019·Annals of the New York Academy of Sciences·José-Carlos Ovando-ZambranoAntony A Boucard
Jan 28, 2020·ELife·Alessandra Sclip, Thomas C Südhof
Jun 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nana MaJun Wan
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