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The composition of EphB2 clusters determines the strength in the cellular repulsion response

Trans interactions of erythropoietin-producing human hepatocellular (Eph) receptors with their membrane-bound ephrin ligands generate higher-order clusters that can form extended signaling arrays. The functional relevance of the cluster size for repulsive signaling is not understood. We used chemica...

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Autores principales: Schaupp, Andreas, Sabet, Ola, Dudanova, Irina, Ponserre, Marion, Bastiaens, Philippe, Klein, Rüdiger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912530/
https://www.ncbi.nlm.nih.gov/pubmed/24469634
http://dx.doi.org/10.1083/jcb.201305037
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author Schaupp, Andreas
Sabet, Ola
Dudanova, Irina
Ponserre, Marion
Bastiaens, Philippe
Klein, Rüdiger
author_facet Schaupp, Andreas
Sabet, Ola
Dudanova, Irina
Ponserre, Marion
Bastiaens, Philippe
Klein, Rüdiger
author_sort Schaupp, Andreas
collection PubMed
description Trans interactions of erythropoietin-producing human hepatocellular (Eph) receptors with their membrane-bound ephrin ligands generate higher-order clusters that can form extended signaling arrays. The functional relevance of the cluster size for repulsive signaling is not understood. We used chemical dimerizers and fluorescence anisotropy to generate and visualize specific EphB2 cluster species in living cells. We find that cell collapse responses are induced by small-sized EphB2 clusters, suggesting that extended EphB2 arrays are dispensable and that EphB2 activation follows an ON–OFF switch with EphB2 dimers being inactive and trimers and tetramers being fully functional. Moreover, the strength of the collapse response is determined by the abundance of multimers over dimers within a cluster population: the more dimers are present, the weaker the response. Finally, we show that the C-terminal modules of EphB2 have negative regulatory effects on ephrin-induced clustering. These results shed new light on the mechanism and regulation of EphB2 activation and provide a model on how Eph signaling translates into graded cellular responses.
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spelling pubmed-39125302014-08-03 The composition of EphB2 clusters determines the strength in the cellular repulsion response Schaupp, Andreas Sabet, Ola Dudanova, Irina Ponserre, Marion Bastiaens, Philippe Klein, Rüdiger J Cell Biol Research Articles Trans interactions of erythropoietin-producing human hepatocellular (Eph) receptors with their membrane-bound ephrin ligands generate higher-order clusters that can form extended signaling arrays. The functional relevance of the cluster size for repulsive signaling is not understood. We used chemical dimerizers and fluorescence anisotropy to generate and visualize specific EphB2 cluster species in living cells. We find that cell collapse responses are induced by small-sized EphB2 clusters, suggesting that extended EphB2 arrays are dispensable and that EphB2 activation follows an ON–OFF switch with EphB2 dimers being inactive and trimers and tetramers being fully functional. Moreover, the strength of the collapse response is determined by the abundance of multimers over dimers within a cluster population: the more dimers are present, the weaker the response. Finally, we show that the C-terminal modules of EphB2 have negative regulatory effects on ephrin-induced clustering. These results shed new light on the mechanism and regulation of EphB2 activation and provide a model on how Eph signaling translates into graded cellular responses. The Rockefeller University Press 2014-02-03 /pmc/articles/PMC3912530/ /pubmed/24469634 http://dx.doi.org/10.1083/jcb.201305037 Text en © 2014 Schaupp et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Schaupp, Andreas
Sabet, Ola
Dudanova, Irina
Ponserre, Marion
Bastiaens, Philippe
Klein, Rüdiger
The composition of EphB2 clusters determines the strength in the cellular repulsion response
title The composition of EphB2 clusters determines the strength in the cellular repulsion response
title_full The composition of EphB2 clusters determines the strength in the cellular repulsion response
title_fullStr The composition of EphB2 clusters determines the strength in the cellular repulsion response
title_full_unstemmed The composition of EphB2 clusters determines the strength in the cellular repulsion response
title_short The composition of EphB2 clusters determines the strength in the cellular repulsion response
title_sort composition of ephb2 clusters determines the strength in the cellular repulsion response
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912530/
https://www.ncbi.nlm.nih.gov/pubmed/24469634
http://dx.doi.org/10.1083/jcb.201305037
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