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Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells

Author

Listed:
  • Iman Lohraseb

    (University of South Australia and SA Pathology)

  • Peter McCarthy

    (University of South Australia and SA Pathology)

  • Genevieve Secker

    (University of South Australia and SA Pathology)

  • Ceilidh Marchant

    (University of South Australia and SA Pathology)

  • Jianmin Wu

    (Garvan Institute of Medical Research
    University of New South Wales)

  • Naveid Ali

    (Garvan Institute of Medical Research)

  • Sharad Kumar

    (University of South Australia and SA Pathology)

  • Roger J. Daly

    (Monash University)

  • Natasha L. Harvey

    (University of South Australia and SA Pathology)

  • Hiroshi Kawabe

    (Max Planck Institute for Experimental Medicine
    Gunma University Graduate School of Medicine)

  • Oded Kleifeld

    (Technion-Israel Institute of Technology)

  • Sophie Wiszniak

    (University of South Australia and SA Pathology)

  • Quenten Schwarz

    (University of South Australia and SA Pathology)

Abstract

The ubiquitin ligase NEDD4 promotes neural crest cell (NCC) survival and stem-cell like properties to regulate craniofacial and peripheral nervous system development. However, how ubiquitination and NEDD4 control NCC development remains unknown. Here we combine quantitative analysis of the proteome, transcriptome and ubiquitinome to identify key developmental signalling pathways that are regulated by NEDD4. We report 276 NEDD4 targets in NCCs and show that loss of NEDD4 leads to a pronounced global reduction in specific ubiquitin lysine linkages. We further show that NEDD4 contributes to the regulation of the NCC actin cytoskeleton by controlling ubiquitination and turnover of Profilin 1 to modulate filamentous actin polymerization. Taken together, our data provide insights into how NEDD4-mediated ubiquitination coordinates key regulatory processes during NCC development.

Suggested Citation

  • Iman Lohraseb & Peter McCarthy & Genevieve Secker & Ceilidh Marchant & Jianmin Wu & Naveid Ali & Sharad Kumar & Roger J. Daly & Natasha L. Harvey & Hiroshi Kawabe & Oded Kleifeld & Sophie Wiszniak & Q, 2022. "Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29660-3
    DOI: 10.1038/s41467-022-29660-3
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    References listed on IDEAS

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    1. Chao Quan & Qian Du & Min Li & Ruizhen Wang & Qian Ouyang & Shu Su & Sangsang Zhu & Qiaoli Chen & Yang Sheng & Liang Chen & Hong Wang & David G. Campbell & Carol MacKintosh & Zhongzhou Yang & Kunfu Ou, 2020. "A PKB-SPEG signaling nexus links insulin resistance with diabetic cardiomyopathy by regulating calcium homeostasis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Toshiaki Fukushima & Hidehito Yoshihara & Haruka Furuta & Hiroyasu Kamei & Fumihiko Hakuno & Jing Luan & Cunming Duan & Yasushi Saeki & Keiji Tanaka & Shun-Ichiro Iemura & Tohru Natsume & Kazuhiro Chi, 2015. "Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
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