The mitotic spindle is a bipolar cellular structure, built from tubulin polymers, called microtubules, and interacting proteins. This macromolecular machine orchestrates chromosome segregation, thereby ensuring accurate distribution of genetic material into the two daughter cells during cell division. Powered by GTP hydrolysis upon tubulin polymerization, the microtubule ends exhibit a metastable behavior known as the dynamic instability, during which they stochastically switch between the growth and shrinkage phases. In the context of the mitotic spindle, dynamic instability is furthermore regulated by microtubule-associated proteins and motor proteins, which enables the spindle to undergo profound changes during mitosis. This highly dynamic behavior is essential for chromosome capture and congression in prometaphase, as well as for chromosome alignment to the spindle equator in metaphase and their segregation in anaphase. In this review we focus on the mechanisms underlying microtubule dynamics and sliding and their importance for the maintenance of shape, structure and dynamics of the metaphase spindle. We discuss how these spindle properties are related to the phenomenon of microtubule poleward flux, highlighting its highly cooperative molecular basis and role in keeping the metaphase spindle at a steady state.
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http://dx.doi.org/10.1016/j.semcdb.2021.05.016 | DOI Listing |
Development
January 2025
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Karyotype instability in the germline leads to infertility. Unlike the female germline, the male germline continuously produces fertile sperm throughout life. Here we present a molecular network responsible for maintaining karyotype stability in the male mouse germline.
View Article and Find Full Text PDFComput Biol Med
January 2025
Center for Cell Dynamics, School of Biological and Behavioural Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, United Kingdom; The Alan Turing Institute, London, NW1 2DB, United Kingdom. Electronic address:
SpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinX's applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
The mitotic spindle is composed of distinct networks of microtubules, including interpolar bundles that can bridge sister kinetochore fibers and bundles that organize the spindle midzone in anaphase. The crosslinking protein PRC1 can mediate such bundling interactions between antiparallel microtubules. PRC1 is a substrate of mitotic kinases including CDK/cyclin-B, suggesting that it can be phosphorylated in metaphase and dephosphorylated in anaphase.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Obstetrics and Prenatal Medicine, Department of Gynecology and Obstetrics, University Hospital Frankfurt, J. W. Goethe-University, Frankfurt, Germany.
The protein regulator of cytokinesis 1 (PRC1) is a key regulator of microtubule crosslinking and bundling, which is crucial for spindle formation and cytokinesis. RITA, the BP-J nteracting and ubulin-ssociated protein, is a microtubule associated protein. We have reported that RITA localizes to mitotic spindles modulating microtubule dynamics and stability as well as to spindle poles affecting the activity of Aurora A.
View Article and Find Full Text PDFEMBO Rep
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Spindle assembly checkpoint (SAC) inhibitors are a recently developed class of drugs, which perturb chromosome segregation during cell division, induce chromosomal instability (CIN), and eventually lead to cell death. The molecular features that determine cellular sensitivity to these drugs are not fully understood. We recently reported that aneuploid cancer cells are preferentially sensitive to SAC inhibition.
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