NHSL3 controls single and collective cell migration through two distinct mechanisms
Abstract The molecular mechanisms underlying cell migration remain incompletely understood. Here, we show that knock-out cells for NHSL3, the most recently identified member of the Nance-Horan Syndrome family, are more persistent than parental cells in single cell migration, but that, in wound heali...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55647-3 |
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| author | Nikita M. Novikov Jinmei Gao Artem I. Fokin Nathalie Rocques Giovanni Chiappetta Karina D. Rysenkova Diego Javier Zea Anna Polesskaya Joelle Vinh Raphael Guerois Alexis M. Gautreau |
| author_facet | Nikita M. Novikov Jinmei Gao Artem I. Fokin Nathalie Rocques Giovanni Chiappetta Karina D. Rysenkova Diego Javier Zea Anna Polesskaya Joelle Vinh Raphael Guerois Alexis M. Gautreau |
| author_sort | Nikita M. Novikov |
| collection | DOAJ |
| description | Abstract The molecular mechanisms underlying cell migration remain incompletely understood. Here, we show that knock-out cells for NHSL3, the most recently identified member of the Nance-Horan Syndrome family, are more persistent than parental cells in single cell migration, but that, in wound healing, follower cells are impaired in their ability to follow leader cells. The NHSL3 locus encodes several isoforms. We identify the partner repertoire of each isoform using proteomics and predict direct partners and their binding sites using an AlphaFold2-based pipeline. Rescue with specific isoforms, and lack of rescue when relevant binding sites are mutated, establish that the interaction of a long isoform with MENA/VASP proteins is critical at cell-cell junctions for collective migration, while the interaction of a short one with 14-3-3θ in lamellipodia is critical for single cell migration. Taken together, these results demonstrate that NHSL3 regulates single and collective cell migration through distinct mechanisms. |
| format | Article |
| id | doaj-art-374e85401adf46df8c4963b599ea584e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-374e85401adf46df8c4963b599ea584e2025-01-05T12:37:31ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-024-55647-3NHSL3 controls single and collective cell migration through two distinct mechanismsNikita M. Novikov0Jinmei Gao1Artem I. Fokin2Nathalie Rocques3Giovanni Chiappetta4Karina D. Rysenkova5Diego Javier Zea6Anna Polesskaya7Joelle Vinh8Raphael Guerois9Alexis M. Gautreau10Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisLaboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisBiological Mass Spectrometry and Proteomics (SMBP), ESPCI Paris, Université PSL, LPC CNRS UMR8249Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisBiological Mass Spectrometry and Proteomics (SMBP), ESPCI Paris, Université PSL, LPC CNRS UMR8249Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC)Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de ParisAbstract The molecular mechanisms underlying cell migration remain incompletely understood. Here, we show that knock-out cells for NHSL3, the most recently identified member of the Nance-Horan Syndrome family, are more persistent than parental cells in single cell migration, but that, in wound healing, follower cells are impaired in their ability to follow leader cells. The NHSL3 locus encodes several isoforms. We identify the partner repertoire of each isoform using proteomics and predict direct partners and their binding sites using an AlphaFold2-based pipeline. Rescue with specific isoforms, and lack of rescue when relevant binding sites are mutated, establish that the interaction of a long isoform with MENA/VASP proteins is critical at cell-cell junctions for collective migration, while the interaction of a short one with 14-3-3θ in lamellipodia is critical for single cell migration. Taken together, these results demonstrate that NHSL3 regulates single and collective cell migration through distinct mechanisms.https://doi.org/10.1038/s41467-024-55647-3 |
| spellingShingle | Nikita M. Novikov Jinmei Gao Artem I. Fokin Nathalie Rocques Giovanni Chiappetta Karina D. Rysenkova Diego Javier Zea Anna Polesskaya Joelle Vinh Raphael Guerois Alexis M. Gautreau NHSL3 controls single and collective cell migration through two distinct mechanisms Nature Communications |
| title | NHSL3 controls single and collective cell migration through two distinct mechanisms |
| title_full | NHSL3 controls single and collective cell migration through two distinct mechanisms |
| title_fullStr | NHSL3 controls single and collective cell migration through two distinct mechanisms |
| title_full_unstemmed | NHSL3 controls single and collective cell migration through two distinct mechanisms |
| title_short | NHSL3 controls single and collective cell migration through two distinct mechanisms |
| title_sort | nhsl3 controls single and collective cell migration through two distinct mechanisms |
| url | https://doi.org/10.1038/s41467-024-55647-3 |
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