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; Quenten Schwarz

doi:10.1038/s41467-022-29660-3

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, Quenten Schwarz

Biology

Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	2018
Pages (from-to)	2018
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29660-3
State	Published - 19 Apr 2022

Keywords

Actins/metabolism
Endosomal Sorting Complexes Required for Transport/metabolism
Nedd4 Ubiquitin Protein Ligases/genetics
Neural Crest/metabolism
Profilins/genetics
Ubiquitin-Protein Ligases/metabolism
Ubiquitin/metabolism
Ubiquitination

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10.1038/s41467-022-29660-3

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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). Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells. Nature Communications, 13(1), 2018. Article 2018. https://doi.org/10.1038/s41467-022-29660-3

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

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.",

keywords = "Actins/metabolism, Endosomal Sorting Complexes Required for Transport/metabolism, Nedd4 Ubiquitin Protein Ligases/genetics, Neural Crest/metabolism, Profilins/genetics, Ubiquitin-Protein Ligases/metabolism, Ubiquitin/metabolism, Ubiquitination",

author = "Iman Lohraseb and Peter McCarthy and Genevieve Secker and Ceilidh Marchant and Jianmin Wu and Naveid Ali and Sharad Kumar and Daly, \{Roger J.\} and Harvey, \{Natasha L.\} and Hiroshi Kawabe and Oded Kleifeld and Sophie Wiszniak and Quenten Schwarz",

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doi = "10.1038/s41467-022-29660-3",

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Lohraseb, I, McCarthy, P, Secker, G, Marchant, C, Wu, J, Ali, N, Kumar, S, Daly, RJ, Harvey, NL, Kawabe, H, Kleifeld, O, Wiszniak, S & Schwarz, Q 2022, 'Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells', Nature Communications, vol. 13, no. 1, 2018, pp. 2018. https://doi.org/10.1038/s41467-022-29660-3

TY - JOUR

T1 - Global ubiquitinome profiling identifies NEDD4 as a regulator of Profilin 1 and actin remodelling in neural crest cells

AU - Lohraseb, Iman

AU - McCarthy, Peter

AU - Secker, Genevieve

AU - Marchant, Ceilidh

AU - Wu, Jianmin

AU - Ali, Naveid

AU - Kumar, Sharad

AU - Daly, Roger J.

AU - Harvey, Natasha L.

AU - Kawabe, Hiroshi

AU - Kleifeld, Oded

AU - Wiszniak, Sophie

AU - Schwarz, Quenten

PY - 2022/4/19

Y1 - 2022/4/19

N2 - 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.

AB - 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.

KW - Actins/metabolism

KW - Endosomal Sorting Complexes Required for Transport/metabolism

KW - Nedd4 Ubiquitin Protein Ligases/genetics

KW - Neural Crest/metabolism

KW - Profilins/genetics

KW - Ubiquitin-Protein Ligases/metabolism

KW - Ubiquitin/metabolism

KW - Ubiquitination

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U2 - 10.1038/s41467-022-29660-3

DO - 10.1038/s41467-022-29660-3

M3 - مقالة

C2 - 35440627

SN - 2041-1723

VL - 13

SP - 2018

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2018

ER -

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

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