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Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex
During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting pa...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073056/ https://www.ncbi.nlm.nih.gov/pubmed/33923443 http://dx.doi.org/10.3390/ijms22084115 |
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author | Simanov, Gleb Dang, Irene Fokin, Artem I. Oguievetskaia, Ksenia Campanacci, Valérie Cherfils, Jacqueline Gautreau, Alexis M. |
author_facet | Simanov, Gleb Dang, Irene Fokin, Artem I. Oguievetskaia, Ksenia Campanacci, Valérie Cherfils, Jacqueline Gautreau, Alexis M. |
author_sort | Simanov, Gleb |
collection | PubMed |
description | During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting partners and identified both Tankyrase 1 and 2 (TNKS) using a yeast two-hybrid screening and coimmunoprecipitation with full-length Arpin as bait. Arpin interacts with ankyrin repeats of TNKS through a C-terminal-binding site on its acidic tail, which overlaps with the Arp2/3-binding site. Arpin was found to dissolve the liquid–liquid phase separation of TNKS upon overexpression. To uncouple the interactions of Arpin with TNKS and Arp2/3, we introduced point mutations in the Arpin tail and attempted to rescue the increased migration persistence of the Arpin knockout cells using random plasmid integration or compensating knock-ins at the ARPIN locus. Arpin mutations impairing interactions with either Arp2/3 or TNKS were insufficient to fully abolish Arpin activity. Only the mutation that affected both interactions rendered Arpin completely inactive, suggesting the existence of two independent pathways, whereby Arpin controls the migration persistence. |
format | Online Article Text |
id | pubmed-8073056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80730562021-04-27 Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex Simanov, Gleb Dang, Irene Fokin, Artem I. Oguievetskaia, Ksenia Campanacci, Valérie Cherfils, Jacqueline Gautreau, Alexis M. Int J Mol Sci Article During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting partners and identified both Tankyrase 1 and 2 (TNKS) using a yeast two-hybrid screening and coimmunoprecipitation with full-length Arpin as bait. Arpin interacts with ankyrin repeats of TNKS through a C-terminal-binding site on its acidic tail, which overlaps with the Arp2/3-binding site. Arpin was found to dissolve the liquid–liquid phase separation of TNKS upon overexpression. To uncouple the interactions of Arpin with TNKS and Arp2/3, we introduced point mutations in the Arpin tail and attempted to rescue the increased migration persistence of the Arpin knockout cells using random plasmid integration or compensating knock-ins at the ARPIN locus. Arpin mutations impairing interactions with either Arp2/3 or TNKS were insufficient to fully abolish Arpin activity. Only the mutation that affected both interactions rendered Arpin completely inactive, suggesting the existence of two independent pathways, whereby Arpin controls the migration persistence. MDPI 2021-04-16 /pmc/articles/PMC8073056/ /pubmed/33923443 http://dx.doi.org/10.3390/ijms22084115 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Simanov, Gleb Dang, Irene Fokin, Artem I. Oguievetskaia, Ksenia Campanacci, Valérie Cherfils, Jacqueline Gautreau, Alexis M. Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title_full | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title_fullStr | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title_full_unstemmed | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title_short | Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex |
title_sort | arpin regulates migration persistence by interacting with both tankyrases and the arp2/3 complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073056/ https://www.ncbi.nlm.nih.gov/pubmed/33923443 http://dx.doi.org/10.3390/ijms22084115 |
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