The Ndc80 complex targets Bod1 to human mitotic kinetochores

Katharina Schleicher, Michael Porter, Sara ten Have, Ramasubramanian Sundaramoorthy, Iain M. Porter, Jason R. Swedlow (Lead / Corresponding author)

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    Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of PP2A-B56. This phosphatase controls the amount of phosphorylation of mitotic kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. The PP2A-B56 regulatory protein Bod1 directly localises to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localisation of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1 binding and inhibition of PP2A-B56, peaks in prometaphase, when PP2A-B56 localisation to kinetochores is highest. Kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Additionally, Bod1 depletion leads to a defect in the phosphorylation kinetics of Ndc80 at serine 55 (S55) within its N-terminus. Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80 phosphorylation and the stability of the attachments of microtubules to kinetochores.
    Original languageEnglish
    Article number170099
    Pages (from-to)1-14
    Number of pages14
    JournalOpen Biology
    Publication statusPublished - 15 Nov 2017


    • Chromosome segregation
    • Kinetochore
    • Bod1
    • PP2A inhibitor
    • Ndc80 complex
    • Kn11


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