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Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones
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 i...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245728/ https://www.ncbi.nlm.nih.gov/pubmed/30457553 http://dx.doi.org/10.7554/eLife.37935 |
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author | Vysokov, Nickolai V Silva, John-Paul Lelianova, Vera G Suckling, Jason Cassidy, John Blackburn, Jennifer K Yankova, Natalia Djamgoz, Mustafa BA Kozlov, Serguei V Tonevitsky, Alexander G Ushkaryov, Yuri A |
author_facet | Vysokov, Nickolai V Silva, John-Paul Lelianova, Vera G Suckling, Jason Cassidy, John Blackburn, Jennifer K Yankova, Natalia Djamgoz, Mustafa BA Kozlov, Serguei V Tonevitsky, Alexander G Ushkaryov, Yuri A |
author_sort | Vysokov, Nickolai V |
collection | PubMed |
description | 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 signaling that induces axonal attraction. |
format | Online Article Text |
id | pubmed-6245728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-62457282018-11-20 Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones Vysokov, Nickolai V Silva, John-Paul Lelianova, Vera G Suckling, Jason Cassidy, John Blackburn, Jennifer K Yankova, Natalia Djamgoz, Mustafa BA Kozlov, Serguei V Tonevitsky, Alexander G Ushkaryov, Yuri A eLife Cell Biology 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 signaling that induces axonal attraction. eLife Sciences Publications, Ltd 2018-11-20 /pmc/articles/PMC6245728/ /pubmed/30457553 http://dx.doi.org/10.7554/eLife.37935 Text en © 2018, Vysokov et al http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Cell Biology Vysokov, Nickolai V Silva, John-Paul Lelianova, Vera G Suckling, Jason Cassidy, John Blackburn, Jennifer K Yankova, Natalia Djamgoz, Mustafa BA Kozlov, Serguei V Tonevitsky, Alexander G Ushkaryov, Yuri A Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title | Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title_full | Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title_fullStr | Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title_full_unstemmed | Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title_short | Proteolytically released Lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
title_sort | proteolytically released lasso/teneurin-2 induces axonal attraction by interacting with latrophilin-1 on axonal growth cones |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245728/ https://www.ncbi.nlm.nih.gov/pubmed/30457553 http://dx.doi.org/10.7554/eLife.37935 |
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