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

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 and Quenten Schwarz ()
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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
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
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

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29660-3

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DOI: 10.1038/s41467-022-29660-3

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