Related Experiment Video

Updated: Jun 28, 2025

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

14.3K

Molecular interplay between HURP and Kif18A in mitotic spindle regulation

Juan M Perez-Bertoldi, Yuanchang Zhao, Akanksha Thawani

    Biorxiv : the Preprint Server for Biology
    |April 22, 2024
    PubMed

    Insights

    Hepatoma-upregulated protein (HURP) regulates kinesin Kif18A motility on microtubules. This interaction, revealed by Cryo-EM, explains how HURP and Kif18A control microtubule dynamics during cell division.

    Area of Science:

    • Cell Biology
    • Molecular Biology
    • Biophysics

    Background:

    • Microtubule dynamics are crucial for chromosome segregation during mitosis.
    • Hepatoma-upregulated protein (HURP) and kinesin Kif18A are key regulators of kinetochore-microtubule interactions.
    • The precise mechanism of their coordinated regulation remained unclear.

    Approach:

    • Utilized single-molecule imaging in vitro to study Kif18A motility.
    • Determined the binding mode of HURP to microtubules using Cryo-Electron Microscopy (Cryo-EM).
    • Investigated the functional interplay between HURP and Kif18A.

    Key Points:

    • HURP concentration-dependently regulates Kif18A motor activity; sparse HURP activates, while high concentrations inhibit.
    • Cryo-EM revealed HURP binds microtubules by spanning across β-tubulin and between protofilaments.
    • HURP binding site partially overlaps Kif18A's microtubule-binding site, suggesting steric hindrance.
    • HURP and Kif18A collaborate to suppress microtubule plus-end dynamics.

    Conclusions:

    • Established a structural and mechanistic basis for HURP's regulation of Kif18A motility.
    • Demonstrated steric exclusion as the mechanism for HURP-mediated Kif18A inhibition.
    • Provided insight into the collective role of HURP and Kif18A in spindle length control.

    More Related Videos

    Directly Measuring Forces Within Reconstituted Active Microtubule Bundles07:47

    Directly Measuring Forces Within Reconstituted Active Microtubule Bundles

    Published on: May 10, 2022

    1.6K
    Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations07:14

    Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations

    Published on: September 20, 2019

    8.2K

    Related Concept Videos

    Destabilization of Microtubules01:45

    Destabilization of Microtubules

    The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
    2.7K
    The Spindle Assembly Checkpoint02:19

    The Spindle Assembly Checkpoint

    The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
    Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
    3.2K
    Anaphase A and B01:39

    Anaphase A and B

    Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
    Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
    4.1K
    Separation of Sister Chromatids02:17

    Separation of Sister Chromatids

    At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
    At the onset of anaphase, separase, a proteolytic enzyme, is...
    3.6K
    Forces Acting on Chromosomes02:11

    Forces Acting on Chromosomes

    During mitosis, chromosome movements occur through the interplay of multiple piconewton level forces. In prometaphase, these forces help in chromosome assembly or congression at the equatorial plane, eventually leading to their alignment at the metaphase plate. The forces acting on the chromosomes are space and time-dependent; therefore, they vary with the position of the chromosomes as the cell progresses through mitosis. 
    Microtubules and motor proteins exert two types of forces on...
    3.3K
    The Mitotic Spindle02:27

    The Mitotic Spindle

    The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
    The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures...
    6.6K