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N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization

Author

Listed:
  • Weiji Weng

    (Shanghai Jiao Tong University School of Medicine)

  • Xiaokun Gu

    (Shanghai Jiao Tong University School of Medicine)

  • Yang Yang

    (Shanghai Jiao Tong University School of Medicine)

  • Qiao Zhang

    (Shanghai Jiao Tong University School of Medicine)

  • Qi Deng

    (Shanghai Jiao Tong University School of Medicine)

  • Jie Zhou

    (Shanghai Jiao Tong University School of Medicine)

  • Jinke Cheng

    (Shanghai Jiao Tong University School of Medicine)

  • Michael X. Zhu

    (The University of Texas Health Science Center at Houston)

  • Junfeng Feng

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Institute of Head Trauma)

  • Ou Huang

    (Shanghai Jiao Tong University School of Medicine)

  • Yong Li

    (Shanghai Jiao Tong University School of Medicine)

Abstract

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.

Suggested Citation

  • Weiji Weng & Xiaokun Gu & Yang Yang & Qiao Zhang & Qi Deng & Jie Zhou & Jinke Cheng & Michael X. Zhu & Junfeng Feng & Ou Huang & Yong Li, 2023. "N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41520-2
    DOI: 10.1038/s41467-023-41520-2
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    References listed on IDEAS

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    1. Yong Kim & Jee Young Sung & Ilaria Ceglia & Ko-Woon Lee & Jung-Hyuck Ahn & Jonathan M. Halford & Amie M. Kim & Seung P. Kwak & Jong Bae Park & Sung Ho Ryu & Annette Schenck & Barbara Bardoni & John D., 2006. "Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology," Nature, Nature, vol. 442(7104), pages 814-817, August.
    2. Mark Hochstrasser, 2009. "Origin and function of ubiquitin-like proteins," Nature, Nature, vol. 458(7237), pages 422-429, March.
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