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)
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Official URL: http:\\dx.doi.org/10.7554/eLife.37935 |
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 |
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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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