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N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization
Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics an...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502023/ https://www.ncbi.nlm.nih.gov/pubmed/37709794 http://dx.doi.org/10.1038/s41467-023-41520-2 |
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author | Weng, Weiji Gu, Xiaokun Yang, Yang Zhang, Qiao Deng, Qi Zhou, Jie Cheng, Jinke Zhu, Michael X. Feng, Junfeng Huang, Ou Li, Yong |
author_facet | Weng, Weiji Gu, Xiaokun Yang, Yang Zhang, Qiao Deng, Qi Zhou, Jie Cheng, Jinke Zhu, Michael X. Feng, Junfeng Huang, Ou Li, Yong |
author_sort | Weng, Weiji |
collection | PubMed |
description | Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics. |
format | Online Article Text |
id | pubmed-10502023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105020232023-09-16 N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization Weng, Weiji Gu, Xiaokun Yang, Yang Zhang, Qiao Deng, Qi Zhou, Jie Cheng, Jinke Zhu, Michael X. Feng, Junfeng Huang, Ou Li, Yong Nat Commun Article Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics. Nature Publishing Group UK 2023-09-14 /pmc/articles/PMC10502023/ /pubmed/37709794 http://dx.doi.org/10.1038/s41467-023-41520-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Weng, Weiji Gu, Xiaokun Yang, Yang Zhang, Qiao Deng, Qi Zhou, Jie Cheng, Jinke Zhu, Michael X. Feng, Junfeng Huang, Ou Li, Yong N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title | N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title_full | N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title_fullStr | N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title_full_unstemmed | N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title_short | N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization |
title_sort | n-terminal α-amino sumoylation of cofilin-1 is critical for its regulation of actin depolymerization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502023/ https://www.ncbi.nlm.nih.gov/pubmed/37709794 http://dx.doi.org/10.1038/s41467-023-41520-2 |
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