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Vogl, A.M.* ; Phu, L.* ; Becerra, R.* ; Giusti, S.A.* ; Verschueren, E.* ; Hinkle, T.B.* ; Bordenave, M.D.* ; Adrian, M.* ; Heidersbach, A.* ; Yankilevich, P.* ; Stefani, F.D.* ; Wurst, W. ; Hoogenraad, C.C.* ; Kirkpatrick, D.S.* ; Refojo, D.* ; Sheng, M.*

Global site-specific neddylation profiling reveals that NEDDylated cofilin regulates actin dynamics.

Nat. Struct. Mol. Biol. 27, 210-220 (2020)
Verlagsversion Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Neddylation is the post-translational protein modification most closely related to ubiquitination. Whereas the ubiquitin-like protein NEDD8 is well studied for its role in activating cullin−RING E3 ubiquitin ligases, little is known about other substrates. We developed serial NEDD8-ubiquitin substrate profiling (sNUSP), a method that employs NEDD8 R74K knock-in HEK293 cells, allowing discrimination of endogenous NEDD8- and ubiquitin-modification sites by MS after Lys-C digestion and K-εGG-peptide enrichment. Using sNUSP, we identified 607 neddylation sites dynamically regulated by the neddylation inhibitor MLN4924 and the de-neddylating enzyme NEDP1, implying that many non-cullin proteins are neddylated. Among the candidates, we characterized lysine 112 of the actin regulator cofilin as a novel neddylation event. Global inhibition of neddylation in developing neurons leads to cytoskeletal defects, altered actin dynamics and neurite growth impairments, whereas site-specific neddylation of cofilin at K112 regulates neurite outgrowth, suggesting that cofilin neddylation contributes to the regulation of neuronal actin organization.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Quellenangaben Band: 27, Heft: 2, Seiten: 210-220 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed