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A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib

Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B...

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Autores principales: Sun, Tianliang, Yang, Lida, Kaur, Harmandeep, Pestel, Jenny, Looso, Mario, Nolte, Hendrik, Krasel, Cornelius, Heil, Daniel, Krishnan, Ramesh K., Santoni, Marie-Josée, Borg, Jean-Paul, Bünemann, Moritz, Offermanns, Stefan, Swiercz, Jakub M., Worzfeld, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223600/
https://www.ncbi.nlm.nih.gov/pubmed/28007914
http://dx.doi.org/10.1083/jcb.201602002
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author Sun, Tianliang
Yang, Lida
Kaur, Harmandeep
Pestel, Jenny
Looso, Mario
Nolte, Hendrik
Krasel, Cornelius
Heil, Daniel
Krishnan, Ramesh K.
Santoni, Marie-Josée
Borg, Jean-Paul
Bünemann, Moritz
Offermanns, Stefan
Swiercz, Jakub M.
Worzfeld, Thomas
author_facet Sun, Tianliang
Yang, Lida
Kaur, Harmandeep
Pestel, Jenny
Looso, Mario
Nolte, Hendrik
Krasel, Cornelius
Heil, Daniel
Krishnan, Ramesh K.
Santoni, Marie-Josée
Borg, Jean-Paul
Bünemann, Moritz
Offermanns, Stefan
Swiercz, Jakub M.
Worzfeld, Thomas
author_sort Sun, Tianliang
collection PubMed
description Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration.
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spelling pubmed-52236002017-07-02 A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib Sun, Tianliang Yang, Lida Kaur, Harmandeep Pestel, Jenny Looso, Mario Nolte, Hendrik Krasel, Cornelius Heil, Daniel Krishnan, Ramesh K. Santoni, Marie-Josée Borg, Jean-Paul Bünemann, Moritz Offermanns, Stefan Swiercz, Jakub M. Worzfeld, Thomas J Cell Biol Research Articles Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A. We further show that binding of Plexin-B1 to Sema4A promotes the interaction of Sema4A with Scrib, thereby removing Scrib from its complex with the Rac/Cdc42 exchange factor βPIX and decreasing the activity of the small guanosine triphosphatase Rac1 and Cdc42. Our data unravel a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A, which controls cell migration. The Rockefeller University Press 2017-01-02 /pmc/articles/PMC5223600/ /pubmed/28007914 http://dx.doi.org/10.1083/jcb.201602002 Text en © 2017 Sun et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Sun, Tianliang
Yang, Lida
Kaur, Harmandeep
Pestel, Jenny
Looso, Mario
Nolte, Hendrik
Krasel, Cornelius
Heil, Daniel
Krishnan, Ramesh K.
Santoni, Marie-Josée
Borg, Jean-Paul
Bünemann, Moritz
Offermanns, Stefan
Swiercz, Jakub M.
Worzfeld, Thomas
A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title_full A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title_fullStr A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title_full_unstemmed A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title_short A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib
title_sort reverse signaling pathway downstream of sema4a controls cell migration via scrib
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223600/
https://www.ncbi.nlm.nih.gov/pubmed/28007914
http://dx.doi.org/10.1083/jcb.201602002
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