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Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration

Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates di...

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Autores principales: Rainero, Elena, Caswell, Patrick T., Muller, Patricia A.J., Grindlay, Joan, McCaffrey, Mary W., Zhang, Qifeng, Wakelam, Michael J.O., Vousden, Karen H., Graziani, Andrea, Norman, Jim C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265946/
https://www.ncbi.nlm.nih.gov/pubmed/22270919
http://dx.doi.org/10.1083/jcb.201109112
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author Rainero, Elena
Caswell, Patrick T.
Muller, Patricia A.J.
Grindlay, Joan
McCaffrey, Mary W.
Zhang, Qifeng
Wakelam, Michael J.O.
Vousden, Karen H.
Graziani, Andrea
Norman, Jim C.
author_facet Rainero, Elena
Caswell, Patrick T.
Muller, Patricia A.J.
Grindlay, Joan
McCaffrey, Mary W.
Zhang, Qifeng
Wakelam, Michael J.O.
Vousden, Karen H.
Graziani, Andrea
Norman, Jim C.
author_sort Rainero, Elena
collection PubMed
description Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates diacylglycerol to phosphatidic acid (PA), was required for RCP to be mobilized to and tethered at the tips of invasive pseudopods and to allow RCP-dependent α5β1 recycling and the resulting invasiveness of tumor cells. Expression of a constitutive-active mutant of DGK-α drove RCP-dependent invasion in the absence of mutant p53 expression or αvβ3 inhibition, and conversely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod tips. These data demonstrate that generation of PA downstream of DGK-α is essential to connect expression of mutant p53s or inhibition of αvβ3 to RCP and for this Rab11 effector to drive the trafficking of α5β1 that is required for tumor cell invasion through three-dimensional matrices.
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spelling pubmed-32659462012-07-23 Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration Rainero, Elena Caswell, Patrick T. Muller, Patricia A.J. Grindlay, Joan McCaffrey, Mary W. Zhang, Qifeng Wakelam, Michael J.O. Vousden, Karen H. Graziani, Andrea Norman, Jim C. J Cell Biol Research Articles Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates diacylglycerol to phosphatidic acid (PA), was required for RCP to be mobilized to and tethered at the tips of invasive pseudopods and to allow RCP-dependent α5β1 recycling and the resulting invasiveness of tumor cells. Expression of a constitutive-active mutant of DGK-α drove RCP-dependent invasion in the absence of mutant p53 expression or αvβ3 inhibition, and conversely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod tips. These data demonstrate that generation of PA downstream of DGK-α is essential to connect expression of mutant p53s or inhibition of αvβ3 to RCP and for this Rab11 effector to drive the trafficking of α5β1 that is required for tumor cell invasion through three-dimensional matrices. The Rockefeller University Press 2012-01-23 /pmc/articles/PMC3265946/ /pubmed/22270919 http://dx.doi.org/10.1083/jcb.201109112 Text en © 2012 Rainero 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
Rainero, Elena
Caswell, Patrick T.
Muller, Patricia A.J.
Grindlay, Joan
McCaffrey, Mary W.
Zhang, Qifeng
Wakelam, Michael J.O.
Vousden, Karen H.
Graziani, Andrea
Norman, Jim C.
Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title_full Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title_fullStr Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title_full_unstemmed Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title_short Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration
title_sort diacylglycerol kinase α controls rcp-dependent integrin trafficking to promote invasive migration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265946/
https://www.ncbi.nlm.nih.gov/pubmed/22270919
http://dx.doi.org/10.1083/jcb.201109112
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