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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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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. |
format | Online Article Text |
id | pubmed-4263450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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