IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53691-7.html
   My bibliography  Save this article

HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics

Author

Listed:
  • Juan M. Perez-Bertoldi

    (University of California)

  • Yuanchang Zhao

    (University of California
    University of California)

  • Akanksha Thawani

    (University of California)

  • Ahmet Yildiz

    (University of California
    University of California
    University of California
    Lawrence Berkeley National Laboratory)

  • Eva Nogales

    (University of California
    Lawrence Berkeley National Laboratory
    University of California)

Abstract

During mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated protein (HURP) and the mitotic kinesin-8 Kif18A, but the underlying mechanism remains elusive. Using single-molecule imaging in vitro, we demonstrate that Kif18A motility is regulated by HURP. While sparse decoration of HURP activates the motor, higher concentrations hinder processive motility. To shed light on this behavior, we determine the binding mode of HURP to microtubules using cryo-EM. The structure helps rationalize why HURP functions as a microtubule stabilizer. Additionally, HURP partially overlaps with the microtubule-binding site of the Kif18A motor domain, indicating that excess HURP inhibits Kif18A motility by steric exclusion. We also observe that HURP and Kif18A function together to suppress dynamics of the microtubule plus-end, providing a mechanistic basis for how they collectively serve in microtubule length control.

Suggested Citation

  • Juan M. Perez-Bertoldi & Yuanchang Zhao & Akanksha Thawani & Ahmet Yildiz & Eva Nogales, 2024. "HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53691-7
    DOI: 10.1038/s41467-024-53691-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53691-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-53691-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Rameen Beroukhim & Craig H. Mermel & Dale Porter & Guo Wei & Soumya Raychaudhuri & Jerry Donovan & Jordi Barretina & Jesse S. Boehm & Jennifer Dobson & Mitsuyoshi Urashima & Kevin T. Mc Henry & Reid M, 2010. "The landscape of somatic copy-number alteration across human cancers," Nature, Nature, vol. 463(7283), pages 899-905, February.
    2. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
    3. Cédric Castrogiovanni & Alessio V. Inchingolo & Jonathan U. Harrison & Damian Dudka & Onur Sen & Nigel J. Burroughs & Andrew D. McAinsh & Patrick Meraldi, 2022. "Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Itxaso Anso & Samira Zouhir & Thibault Géry Sana & Petya Violinova Krasteva, 2024. "Structural basis for synthase activation and cellulose modification in the E. coli Type II Bcs secretion system," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Paloma García Casas & Michela Rossini & Linnea Påvénius & Mezida Saeed & Nikita Arnst & Sonia Sonda & Tânia Fernandes & Irene D’Arsiè & Matteo Bruzzone & Valeria Berno & Andrea Raimondi & Maria Livia , 2024. "Simultaneous detection of membrane contact dynamics and associated Ca2+ signals by reversible chemogenetic reporters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Jidong Fei & Dongdong Zhao & Caiyi Pang & Ju Li & Siwei Li & Wentao Qiao & Juan Tan & Changhao Bi & Xueli Zhang, 2025. "Mismatch prime editing gRNA increased efficiency and reduced indels," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    4. Sebastien Martinez & Shifei Wu & Michael Geuenich & Ahmad Malik & Ramona Weber & Tristan Woo & Amy Zhang & Gun Ho Jang & Dzana Dervovic & Khalid N. Al-Zahrani & Ricky Tsai & Nassima Fodil & Philippe G, 2024. "In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Huiyu Cai & Zuobai Zhang & Mingkai Wang & Bozitao Zhong & Quanxiao Li & Yuxuan Zhong & Yanling Wu & Tianlei Ying & Jian Tang, 2024. "Pretrainable geometric graph neural network for antibody affinity maturation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Anete Romanauska & Edvinas Stankunas & Maya Schuldiner & Alwin Köhler, 2024. "Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Andrea Lopez & Denis E. Reyna & Nadege Gitego & Felix Kopp & Hua Zhou & Miguel A. Miranda-Roman & Lars Ulrik Nordstrøm & Swathi-Rao Narayanagari & Ping Chi & Eduardo Vilar & Aristotelis Tsirigos & Evr, 2022. "Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Nathalie Béchon & Nitzan Tal & Avigail Stokar-Avihail & Alon Savidor & Meital Kupervaser & Sarah Melamed & Gil Amitai & Rotem Sorek, 2024. "Diversification of molecular pattern recognition in bacterial NLR-like proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Jason Saba & Katia Flores & Bailey Marshall & Michael D. Engstrom & Yikai Peng & Atharv S. Garje & Laurie E. Comstock & Robert Landick, 2024. "Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Amika Singla & Daniel J. Boesch & Ho Yee Joyce Fung & Chigozie Ngoka & Avery S. Enriquez & Ran Song & Daniel A. Kramer & Yan Han & Esther Banarer & Andrew Lemoff & Puneet Juneja & Daniel D. Billadeau , 2024. "Structural basis for Retriever-SNX17 assembly and endosomal sorting," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Sanghyeon Choi & Youngjin Lee & Shinhye Park & Song Yee Jang & Jongbin Park & Do Won Oh & Su-Man Kim & Tae-Hwan Kim & Ga Seul Lee & Changyi Cho & Byoung Sik Kim & Donghan Lee & Eun-Hee Kim & Hae-Kap C, 2024. "Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    12. Athira Saju & Po-Pang Chen & Tzu-Han Weng & Su-Yi Tsai & Akihiro Tanaka & Yu-Ting Tseng & Chih-Chia Chang & Chun-Hsiung Wang & Yuta Shimamoto & Kuo-Chiang Hsia, 2024. "HURP binding to the vinca domain of β-tubulin accounts for cancer drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    13. Yijia Cheng & Mark A. B. Kreutzberger & Jianting Han & Edward H. Egelman & Qin Cao, 2024. "Molecular architecture of the assembly of Bacillus spore coat protein GerQ revealed by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    14. Leishu Lin & Jiayuan Dong & Shun Xu & Jinman Xiao & Cong Yu & Fengfeng Niu & Zhiyi Wei, 2024. "Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Yanyi Song & Shuyi Jian & Junlin Teng & Pengli Zheng & Zhe Zhang, 2025. "Structural basis of human VANGL-PRICKLE interaction," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    16. Venecia Alexandria Valdez & Meisheng Ma & Bernardo Gouveia & Rui Zhang & Sabine Petry, 2024. "HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    17. Michael Kugler & Felix J. Metzner & Gregor Witte & Karl-Peter Hopfner & Katja Lammens, 2024. "Phosphorylation-mediated conformational change regulates human SLFN11," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Jiawei Ge & Ting Wang & Hongwei Yu & Lidan Ye, 2025. "De novo biosynthesis of nylon 12 monomer ω-aminododecanoic acid," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    19. Helena E. Sverak & Luke N. Yaeger & Liam J. Worrall & Condurache M. Vacariu & Amy J. Glenwright & Marija Vuckovic & Zayni-Dean Al Azawi & Ryan P. Lamers & Victoria A. Marko & Clarissa Skorupski & Arvi, 2024. "Cryo-EM characterization of the anydromuropeptide permease AmpG central to bacterial fitness and β-lactam antibiotic resistance," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    20. Fabian Ries & Jasmin Gorlt & Sabrina Kaiser & Vanessa Scherer & Charlotte Seydel & Sandra Nguyen & Andreas Klingl & Julia Legen & Christian Schmitz-Linneweber & Hinrik Plaggenborg & Jediael Z. Y. Ng &, 2025. "A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53691-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.