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GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration

ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of mu...

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Autores principales: Abbruzzese, Genevieve, Cousin, Hélène, Salicioni, Ana Maria, Alfandari, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263450/
https://www.ncbi.nlm.nih.gov/pubmed/25298404
http://dx.doi.org/10.1091/mbc.E14-05-0970
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author Abbruzzese, Genevieve
Cousin, Hélène
Salicioni, Ana Maria
Alfandari, Dominique
author_facet Abbruzzese, Genevieve
Cousin, Hélène
Salicioni, Ana Maria
Alfandari, Dominique
author_sort Abbruzzese, Genevieve
collection PubMed
description ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13.
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spelling pubmed-42634502015-03-02 GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration Abbruzzese, Genevieve Cousin, Hélène Salicioni, Ana Maria Alfandari, Dominique Mol Biol Cell Articles ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13. The American Society for Cell Biology 2014-12-15 /pmc/articles/PMC4263450/ /pubmed/25298404 http://dx.doi.org/10.1091/mbc.E14-05-0970 Text en © 2014 Abbruzzese, Cousin, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Abbruzzese, Genevieve
Cousin, Hélène
Salicioni, Ana Maria
Alfandari, Dominique
GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title_full GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title_fullStr GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title_full_unstemmed GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title_short GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration
title_sort gsk3 and polo-like kinase regulate adam13 function during cranial neural crest cell migration
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263450/
https://www.ncbi.nlm.nih.gov/pubmed/25298404
http://dx.doi.org/10.1091/mbc.E14-05-0970
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