Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor
Nuclear actin polymerization was reported to control different nuclear processes, but its regulation is poorly understood. Here, we show that N-WASP can trigger the formation of nuclear N-WASP/F-actin nodules. While a cancer hotspot mutant of N-WASP lacking the VCA domain (V418fs) had a dominant neg...
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2025-01-01
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| author | Xin Jiang Purusottam Mohapatra Maria Rossing Wenqian Zheng Olga Zbodakova Jayashree Vijay Thatte Claus Storgaard Sørensen Thu Han Le Phan Cord Brakebusch |
| author_facet | Xin Jiang Purusottam Mohapatra Maria Rossing Wenqian Zheng Olga Zbodakova Jayashree Vijay Thatte Claus Storgaard Sørensen Thu Han Le Phan Cord Brakebusch |
| author_sort | Xin Jiang |
| collection | DOAJ |
| description | Nuclear actin polymerization was reported to control different nuclear processes, but its regulation is poorly understood. Here, we show that N-WASP can trigger the formation of nuclear N-WASP/F-actin nodules. While a cancer hotspot mutant of N-WASP lacking the VCA domain (V418fs) had a dominant negative function on nuclear F-actin, an even shorter truncation mutant found in melanoma (R128*) strongly promoted nuclear actin polymerization. Nuclear localization of N-WASP was not regulated by the cell cycle and increasing nuclear F-actin formation by N-WASP had no obvious influence on replication. However, nuclear N-WASP/F-actin nodules colocalized partially with RNA Pol II clusters. N-WASP-dependent actin polymerization promoted the maturation of RNA Pol II clusters, with the short truncation mutant R128* unexpectedly showing the strongest effect. Nuclear N-WASP nodules including V418fs colocalized with WIP and cortactin. Importantly, cortactin binding was essential but not sufficient for F-actin formation, while WIP binding was required for actin polymerization by R128*. These data reveal a cortactin-dependent role for N-WASP in the regulation of nuclear F-actin and indicate contrasting nuclear effects for N-WASP mutants found in cancer. |
| format | Article |
| id | doaj-art-f06c0c90380149f5bec30bac0b2d049f |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-f06c0c90380149f5bec30bac0b2d049f2025-01-10T13:16:24ZengMDPI AGCells2073-44092025-01-011415910.3390/cells14010059Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential FactorXin Jiang0Purusottam Mohapatra1Maria Rossing2Wenqian Zheng3Olga Zbodakova4Jayashree Vijay Thatte5Claus Storgaard Sørensen6Thu Han Le Phan7Cord Brakebusch8Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkCenter for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkBiotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, DenmarkNuclear actin polymerization was reported to control different nuclear processes, but its regulation is poorly understood. Here, we show that N-WASP can trigger the formation of nuclear N-WASP/F-actin nodules. While a cancer hotspot mutant of N-WASP lacking the VCA domain (V418fs) had a dominant negative function on nuclear F-actin, an even shorter truncation mutant found in melanoma (R128*) strongly promoted nuclear actin polymerization. Nuclear localization of N-WASP was not regulated by the cell cycle and increasing nuclear F-actin formation by N-WASP had no obvious influence on replication. However, nuclear N-WASP/F-actin nodules colocalized partially with RNA Pol II clusters. N-WASP-dependent actin polymerization promoted the maturation of RNA Pol II clusters, with the short truncation mutant R128* unexpectedly showing the strongest effect. Nuclear N-WASP nodules including V418fs colocalized with WIP and cortactin. Importantly, cortactin binding was essential but not sufficient for F-actin formation, while WIP binding was required for actin polymerization by R128*. These data reveal a cortactin-dependent role for N-WASP in the regulation of nuclear F-actin and indicate contrasting nuclear effects for N-WASP mutants found in cancer.https://www.mdpi.com/2073-4409/14/1/59nuclear F-actinN-WASPcortactin |
| spellingShingle | Xin Jiang Purusottam Mohapatra Maria Rossing Wenqian Zheng Olga Zbodakova Jayashree Vijay Thatte Claus Storgaard Sørensen Thu Han Le Phan Cord Brakebusch Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor Cells nuclear F-actin N-WASP cortactin |
| title | Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor |
| title_full | Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor |
| title_fullStr | Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor |
| title_full_unstemmed | Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor |
| title_short | Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor |
| title_sort | nuclear n wasp induces actin polymerization in the nucleus with cortactin as an essential factor |
| topic | nuclear F-actin N-WASP cortactin |
| url | https://www.mdpi.com/2073-4409/14/1/59 |
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