HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission
Abscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis. Recently,...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/7/684 |
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| author | Alessandra Pisciottani Loredana Biancolillo Manuela Ferrara Davide Valente Francesca Sardina Laura Monteonofrio Serena Camerini Marco Crescenzi Silvia Soddu Cinzia Rinaldo |
| author_facet | Alessandra Pisciottani Loredana Biancolillo Manuela Ferrara Davide Valente Francesca Sardina Laura Monteonofrio Serena Camerini Marco Crescenzi Silvia Soddu Cinzia Rinaldo |
| author_sort | Alessandra Pisciottani |
| collection | DOAJ |
| description | Abscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis. Recently, we demonstrated that HIPK2, a multifunctional kinase involved in several cellular pathways, contributes to abscission and prevents tetraploidization. Here, we show that HIPK2 binds and phosphorylates spastin at serine 268. During cytokinesis, the midbody-localized spastin is phosphorylated at S268 in HIPK2-proficient cells. In contrast, no spastin is detectable at the midbody in HIPK2-depleted cells. The non-phosphorylatable spastin-S268A mutant does not localize at the midbody and cannot rescue HIPK2-depleted cells from abscission defects. In contrast, the phosphomimetic spastin-S268D mutant localizes at the midbody and restores successful abscission in the HIPK2-depleted cells. These results show that spastin is a novel target of HIPK2 and that HIPK2-mediated phosphorylation of spastin contributes to its midbody localization for successful abscission. |
| first_indexed | 2024-03-12T08:24:34Z |
| format | Article |
| id | doaj.art-6531ac2d6bdd465fbaf46d6702cd73a1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:24:34Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6531ac2d6bdd465fbaf46d6702cd73a12023-09-02T18:11:35ZengMDPI AGCells2073-44092019-07-018768410.3390/cells8070684cells8070684HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for AbscissionAlessandra Pisciottani0Loredana Biancolillo1Manuela Ferrara2Davide Valente3Francesca Sardina4Laura Monteonofrio5Serena Camerini6Marco Crescenzi7Silvia Soddu8Cinzia Rinaldo9Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyCore Facilities, Italian National Institute of Health, 00161 Rome, ItalyCore Facilities, Italian National Institute of Health, 00161 Rome, ItalyUnit of Cellular Networks and Molecular Therapeutic Targets; IRCCS-Regina Elena National Cancer Institute, 00144 Rome, ItalyInstitute of Molecular Biology and Pathology (IBPM), National Research Council (CNR), c/o Sapienza University, 00185 Rome, ItalyAbscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis. Recently, we demonstrated that HIPK2, a multifunctional kinase involved in several cellular pathways, contributes to abscission and prevents tetraploidization. Here, we show that HIPK2 binds and phosphorylates spastin at serine 268. During cytokinesis, the midbody-localized spastin is phosphorylated at S268 in HIPK2-proficient cells. In contrast, no spastin is detectable at the midbody in HIPK2-depleted cells. The non-phosphorylatable spastin-S268A mutant does not localize at the midbody and cannot rescue HIPK2-depleted cells from abscission defects. In contrast, the phosphomimetic spastin-S268D mutant localizes at the midbody and restores successful abscission in the HIPK2-depleted cells. These results show that spastin is a novel target of HIPK2 and that HIPK2-mediated phosphorylation of spastin contributes to its midbody localization for successful abscission.https://www.mdpi.com/2073-4409/8/7/684HIPK2spastinabscissionmidbodyphosphorylation |
| spellingShingle | Alessandra Pisciottani Loredana Biancolillo Manuela Ferrara Davide Valente Francesca Sardina Laura Monteonofrio Serena Camerini Marco Crescenzi Silvia Soddu Cinzia Rinaldo HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission Cells HIPK2 spastin abscission midbody phosphorylation |
| title | HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission |
| title_full | HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission |
| title_fullStr | HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission |
| title_full_unstemmed | HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission |
| title_short | HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission |
| title_sort | hipk2 phosphorylates the microtubule severing enzyme spastin at s268 for abscission |
| topic | HIPK2 spastin abscission midbody phosphorylation |
| url | https://www.mdpi.com/2073-4409/8/7/684 |
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