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Article

Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor

by
Xin Jiang
1,
Purusottam Mohapatra
1,
Maria Rossing
2,3,
Wenqian Zheng
1,
Olga Zbodakova
1,
Jayashree Vijay Thatte
1,
Claus Storgaard Sørensen
1,
Thu Han Le Phan
1 and
Cord Brakebusch
1,*
1
Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaløes Vej5, 2200 Copenhagen, Denmark
2
Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
3
Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Cells 2025, 14(1), 59; https://doi.org/10.3390/cells14010059
Submission received: 29 November 2024 / Revised: 19 December 2024 / Accepted: 26 December 2024 / Published: 6 January 2025
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Abstract

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.
Keywords: nuclear F-actin; N-WASP; cortactin nuclear F-actin; N-WASP; cortactin

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MDPI and ACS Style

Jiang, X.; Mohapatra, P.; Rossing, M.; Zheng, W.; Zbodakova, O.; Thatte, J.V.; Sørensen, C.S.; Le Phan, T.H.; Brakebusch, C. Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor. Cells 2025, 14, 59. https://doi.org/10.3390/cells14010059

AMA Style

Jiang X, Mohapatra P, Rossing M, Zheng W, Zbodakova O, Thatte JV, Sørensen CS, Le Phan TH, Brakebusch C. Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor. Cells. 2025; 14(1):59. https://doi.org/10.3390/cells14010059

Chicago/Turabian Style

Jiang, Xin, Purusottam Mohapatra, Maria Rossing, Wenqian Zheng, Olga Zbodakova, Jayashree Vijay Thatte, Claus Storgaard Sørensen, Thu Han Le Phan, and Cord Brakebusch. 2025. "Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor" Cells 14, no. 1: 59. https://doi.org/10.3390/cells14010059

APA Style

Jiang, X., Mohapatra, P., Rossing, M., Zheng, W., Zbodakova, O., Thatte, J. V., Sørensen, C. S., Le Phan, T. H., & Brakebusch, C. (2025). Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor. Cells, 14(1), 59. https://doi.org/10.3390/cells14010059

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