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The Mechanism of Regulated Release of Lasso/Teneurin-2

Teneurins are large cell-surface receptors involved in axon guidance. Teneurin-2 (also known as latrophilin-1-associated synaptic surface organizer (Lasso)) interacts across the synaptic cleft with presynaptic latrophilin-1, an adhesion G-protein-coupled receptor that participates in regulating neur...

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Autores principales: Vysokov, Nickolai V., Silva, John-Paul, Lelianova, Vera G., Ho, Claudia, Djamgoz, Mustafa B., Tonevitsky, Alexander G., Ushkaryov, Yuri A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956664/
https://www.ncbi.nlm.nih.gov/pubmed/27499734
http://dx.doi.org/10.3389/fnmol.2016.00059
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author Vysokov, Nickolai V.
Silva, John-Paul
Lelianova, Vera G.
Ho, Claudia
Djamgoz, Mustafa B.
Tonevitsky, Alexander G.
Ushkaryov, Yuri A.
author_facet Vysokov, Nickolai V.
Silva, John-Paul
Lelianova, Vera G.
Ho, Claudia
Djamgoz, Mustafa B.
Tonevitsky, Alexander G.
Ushkaryov, Yuri A.
author_sort Vysokov, Nickolai V.
collection PubMed
description Teneurins are large cell-surface receptors involved in axon guidance. Teneurin-2 (also known as latrophilin-1-associated synaptic surface organizer (Lasso)) interacts across the synaptic cleft with presynaptic latrophilin-1, an adhesion G-protein-coupled receptor that participates in regulating neurotransmitter release. Lasso-latrophilin-1 interaction mediates synapse formation and calcium signaling, highlighting the important role of this trans-synaptic receptor pair. However, Lasso is thought to be proteolytically cleaved within its ectodomain and released into the medium, making it unclear whether it acts as a proper cell-surface receptor or a soluble protein. We demonstrate here that during its intracellular processing Lasso is constitutively cleaved at a furin site within its ectodomain. The cleaved fragment, which encompasses almost the entire ectodomain of Lasso, is potentially soluble; however, it remains anchored on the cell surface via its non-covalent interaction with the transmembrane fragment of Lasso. Lasso is also constitutively cleaved within the intracellular domain (ICD). Finally, Lasso can be further proteolytically cleaved within the transmembrane domain. The third cleavage is regulated and releases the entire ectodomain of Lasso into the medium. The released ectodomain of Lasso retains its functional properties and binds latrophilin-1 expressed on other cells; this binding stimulates intracellular Ca(2+) signaling in the target cells. Thus, Lasso not only serves as a bona fide cell-surface receptor, but also as a partially released target-derived signaling factor.
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spelling pubmed-49566642016-08-05 The Mechanism of Regulated Release of Lasso/Teneurin-2 Vysokov, Nickolai V. Silva, John-Paul Lelianova, Vera G. Ho, Claudia Djamgoz, Mustafa B. Tonevitsky, Alexander G. Ushkaryov, Yuri A. Front Mol Neurosci Neuroscience Teneurins are large cell-surface receptors involved in axon guidance. Teneurin-2 (also known as latrophilin-1-associated synaptic surface organizer (Lasso)) interacts across the synaptic cleft with presynaptic latrophilin-1, an adhesion G-protein-coupled receptor that participates in regulating neurotransmitter release. Lasso-latrophilin-1 interaction mediates synapse formation and calcium signaling, highlighting the important role of this trans-synaptic receptor pair. However, Lasso is thought to be proteolytically cleaved within its ectodomain and released into the medium, making it unclear whether it acts as a proper cell-surface receptor or a soluble protein. We demonstrate here that during its intracellular processing Lasso is constitutively cleaved at a furin site within its ectodomain. The cleaved fragment, which encompasses almost the entire ectodomain of Lasso, is potentially soluble; however, it remains anchored on the cell surface via its non-covalent interaction with the transmembrane fragment of Lasso. Lasso is also constitutively cleaved within the intracellular domain (ICD). Finally, Lasso can be further proteolytically cleaved within the transmembrane domain. The third cleavage is regulated and releases the entire ectodomain of Lasso into the medium. The released ectodomain of Lasso retains its functional properties and binds latrophilin-1 expressed on other cells; this binding stimulates intracellular Ca(2+) signaling in the target cells. Thus, Lasso not only serves as a bona fide cell-surface receptor, but also as a partially released target-derived signaling factor. Frontiers Media S.A. 2016-07-22 /pmc/articles/PMC4956664/ /pubmed/27499734 http://dx.doi.org/10.3389/fnmol.2016.00059 Text en Copyright © 2016 Vysokov, Silva, Lelianova, Ho, Djamgoz, Tonevitsky and Ushkaryov. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Vysokov, Nickolai V.
Silva, John-Paul
Lelianova, Vera G.
Ho, Claudia
Djamgoz, Mustafa B.
Tonevitsky, Alexander G.
Ushkaryov, Yuri A.
The Mechanism of Regulated Release of Lasso/Teneurin-2
title The Mechanism of Regulated Release of Lasso/Teneurin-2
title_full The Mechanism of Regulated Release of Lasso/Teneurin-2
title_fullStr The Mechanism of Regulated Release of Lasso/Teneurin-2
title_full_unstemmed The Mechanism of Regulated Release of Lasso/Teneurin-2
title_short The Mechanism of Regulated Release of Lasso/Teneurin-2
title_sort mechanism of regulated release of lasso/teneurin-2
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956664/
https://www.ncbi.nlm.nih.gov/pubmed/27499734
http://dx.doi.org/10.3389/fnmol.2016.00059
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