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Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on growth cones

Vysokov, Nickolai V., Silva, John-Paul, Lelianova, Vera G, Suckling, Jason, Cassidy, John, Blackburn, Jennifer K., Yankova, Natalia, Djamgoz, Mustafa B., Kozlov, Serguei, Tonevitsky, Alexander G., and others. (2018) Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on growth cones. eLife, (7). Article Number 37935. ISSN 2050-084X. E-ISSN 2050-084X. (doi:10.7554/eLife.37935) (KAR id:69740)

Abstract

A presynaptic adhesion G-protein-coupled receptor, latrophilin-1, and a postsynaptic transmembrane protein, Lasso/teneurin-2, are implicated in trans-synaptic interaction that contributes to synapse formation. Surprisingly, during neuronal development, a substantial proportion of Lasso is released into the intercellular space by regulated proteolysis, potentially precluding its function in synaptogenesis. We found that released Lasso binds to cell-surface latrophilin-1 on axonal growth cones. Using microfluidic devices to create stable gradients of soluble Lasso, we show that it induces axonal attraction, without increasing neurite outgrowth. Using latrophilin-1 knockout in mice, we demonstrate that latrophilin-1 is required for this effect. After binding latrophilin-1, Lasso causes downstream signaling, which leads to an increase in cytosolic calcium and enhanced exocytosis, processes that are known to mediate growth cone steering. These findings reveal a novel mechanism of axonal pathfinding, whereby latrophilin-1 and Lasso mediate both short-range interaction that supports synaptogenesis, and long-range signalling that induces axonal attraction.

Item Type: Article
DOI/Identification number: 10.7554/eLife.37935
Uncontrolled keywords: axon attraction, axon guidance, Lasso, latrophilin, teneurin-2, Medway school of pharmacy
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Yuri Ushkarev
Date Deposited: 22 Oct 2018 08:44 UTC
Last Modified: 17 Jan 2024 20:36 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/69740 (The current URI for this page, for reference purposes)

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