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Spa2 remodels ADP-actin via molecular condensation under glucose starvation

Author

Listed:
  • Qianqian Ma

    (Nanyang Technological University)

  • Wahyu Surya

    (Nanyang Technological University)

  • Danxia He

    (Nanyang Technological University)

  • Hanmeng Yang

    (Nanyang Technological University)

  • Xiao Han

    (Nanyang Technological University)

  • Mui Hoon Nai

    (National University of Singapore)

  • Chwee Teck Lim

    (National University of Singapore
    National University of Singapore)

  • Jaume Torres

    (Nanyang Technological University)

  • Yansong Miao

    (Nanyang Technological University
    Nanyang Technological University)

Abstract

Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity.

Suggested Citation

  • Qianqian Ma & Wahyu Surya & Danxia He & Hanmeng Yang & Xiao Han & Mui Hoon Nai & Chwee Teck Lim & Jaume Torres & Yansong Miao, 2024. "Spa2 remodels ADP-actin via molecular condensation under glucose starvation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48863-4
    DOI: 10.1038/s41467-024-48863-4
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    References listed on IDEAS

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