Lohraseb, I.McCarthy, P.Secker, G.Marchant, C.Wu, J.Ali, N.Kumar, S.Daly, R.J.Harvey, N.L.Kawabe, H.Kleifeld, O.Wiszniak, S.Schwarz, Q.2022-10-192022-10-192022Nature Communications, 2022; 13(1):1-182041-17232041-1723https://hdl.handle.net/2440/136675The 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.en© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.Cell signalling; Embryology; Proteomics; UbiquitylationNeural CrestActinsUbiquitin-Protein LigasesUbiquitinProfilinsUbiquitinationEndosomal Sorting Complexes Required for TransportNedd4 Ubiquitin Protein LigasesJournal article10.1038/s41467-022-29660-32022-10-19609155Kumar, S. [0000-0001-7126-9814]Harvey, N.L. [0000-0001-9839-8966]