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CLASP-mediated competitive binding in protein condensates directs microtubule growth

Author

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  • Xuanyan Jia

    (Shenzhen Key Laboratory of Biomolecular Assembling and Regulation
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Leishu Lin

    (Shenzhen Key Laboratory of Biomolecular Assembling and Regulation
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Siqi Guo

    (Southern University of Science and Technology)

  • Lulu Zhou

    (Southern University of Science and Technology)

  • Gaowei Jin

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Jiayuan Dong

    (Shenzhen Key Laboratory of Biomolecular Assembling and Regulation
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Jinman Xiao

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Xingqiao Xie

    (Shenzhen Key Laboratory of Biomolecular Assembling and Regulation
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Yiming Li

    (Southern University of Science and Technology)

  • Sicong He

    (Southern University of Science and Technology)

  • Zhiyi Wei

    (Shenzhen Key Laboratory of Biomolecular Assembling and Regulation
    Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Cong Yu

    (Southern University of Science and Technology
    Southern University of Science and Technology
    and Shenzhen Key Laboratory of Cell Microenvironment)

Abstract

Microtubule organization in cells relies on targeting mechanisms. Cytoplasmic linker proteins (CLIPs) and CLIP-associated proteins (CLASPs) are key regulators of microtubule organization, yet the underlying mechanisms remain elusive. Here, we reveal that the C-terminal domain of CLASP2 interacts with a common motif found in several CLASP-binding proteins. This interaction drives the dynamic localization of CLASP2 to distinct cellular compartments, where CLASP2 accumulates in protein condensates at the cell cortex or the microtubule plus end. These condensates physically contact each other via CLASP2-mediated competitive binding, determining cortical microtubule targeting. The phosphorylation of CLASP2 modulates the dynamics of the condensate-condensate interaction and spatiotemporally navigates microtubule growth. Moreover, we identify additional CLASP-interacting proteins that are involved in condensate contacts in a CLASP2-dependent manner, uncovering a general mechanism governing microtubule targeting. Our findings not only unveil a tunable multiphase system regulating microtubule organization, but also offer general mechanistic insights into intricate protein-protein interactions at the mesoscale level.

Suggested Citation

  • Xuanyan Jia & Leishu Lin & Siqi Guo & Lulu Zhou & Gaowei Jin & Jiayuan Dong & Jinman Xiao & Xingqiao Xie & Yiming Li & Sicong He & Zhiyi Wei & Cong Yu, 2024. "CLASP-mediated competitive binding in protein condensates directs microtubule growth," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50863-3
    DOI: 10.1038/s41467-024-50863-3
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    References listed on IDEAS

    as
    1. Charles Coutton & Alexandra S. Vargas & Amir Amiri-Yekta & Zine-Eddine Kherraf & Selima Fourati Mustapha & Pauline Tanno & Clémentine Wambergue-Legrand & Thomas Karaouzène & Guillaume Martinez & Serge, 2018. "Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
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    3. Chris Ambrose & Jun F. Allard & Eric N. Cytrynbaum & Geoffrey O. Wasteneys, 2011. "A CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis," Nature Communications, Nature, vol. 2(1), pages 1-12, September.
    4. Nathan A. McDonald & Richard D. Fetter & Kang Shen, 2020. "Assembly of synaptic active zones requires phase separation of scaffold molecules," Nature, Nature, vol. 588(7838), pages 454-458, December.
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