Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a
Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migrat...
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| Format: | Article |
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eLife Sciences Publications Ltd
2017-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/26898 |
| _version_ | 1811200289953284096 |
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| author | Vikram Khedgikar Genevieve Abbruzzese Ketan Mathavan Hannah Szydlo Helene Cousin Dominique Alfandari |
| author_facet | Vikram Khedgikar Genevieve Abbruzzese Ketan Mathavan Hannah Szydlo Helene Cousin Dominique Alfandari |
| author_sort | Vikram Khedgikar |
| collection | DOAJ |
| description | Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration. |
| first_indexed | 2024-04-12T02:02:20Z |
| format | Article |
| id | doaj.art-3f7ad04f881843929722f9ce8c307970 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:02:20Z |
| publishDate | 2017-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3f7ad04f881843929722f9ce8c3079702022-12-22T03:52:39ZengeLife Sciences Publications LtdeLife2050-084X2017-08-01610.7554/eLife.26898Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3aVikram Khedgikar0Genevieve Abbruzzese1Ketan Mathavan2Hannah Szydlo3Helene Cousin4Dominique Alfandari5https://orcid.org/0000-0002-0557-1246Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United StatesDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United States; Molecular and Cellular Biology graduate program, University of Massachusetts, Amherst, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United StatesDepartment of Veterinary and Animal Sciences, University of Massachusetts, Amherst, United States; Molecular and Cellular Biology graduate program, University of Massachusetts, Amherst, United StatesAdam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.https://elifesciences.org/articles/26898neural crestADAMmetalloproteaseprotocadherincell migrationembryo |
| spellingShingle | Vikram Khedgikar Genevieve Abbruzzese Ketan Mathavan Hannah Szydlo Helene Cousin Dominique Alfandari Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a eLife neural crest ADAM metalloprotease protocadherin cell migration embryo |
| title | Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a |
| title_full | Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a |
| title_fullStr | Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a |
| title_full_unstemmed | Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a |
| title_short | Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a |
| title_sort | dual control of pcdh8l pcns expression and function in xenopus laevis neural crest cells by adam13 33 via the transcription factors tfap2α and arid3a |
| topic | neural crest ADAM metalloprotease protocadherin cell migration embryo |
| url | https://elifesciences.org/articles/26898 |
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