During anaphase, mitotic spindles elongate up to five times their metaphase length. This process, known as anaphase B, is essential for correct segregation of chromosomes. Here, we examine the control of spindle length during anaphase in the budding yeast Saccharomyces cerevisiae. We show that microtubule stabilization during anaphase requires the microtubule-associated protein Stu2. We further show that the activity of Stu2 is opposed by the activity of the kinesin-related protein Kip3. Reexamination of the kinesin homology tree suggests that KIP3 is the S. cerevisiae orthologue of the microtubule-destabilizing subfamily of kinesins (Kin I). We conclude that a balance of activity between evolutionally conserved microtubule-stabilizing and microtubule-destabilizing factors is essential for correct spindle elongation during anaphase B.
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http://dx.doi.org/10.1083/jcb.153.2.435 | DOI Listing |
J Cell Biol
March 2025
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, China.
TPX2 is an elongated molecule containing multiple α-helical repeats. It stabilizes microtubules (MTs), promotes MT nucleation, and is essential for spindle assembly. However, the molecular basis of how TPX2 performs these functions remains elusive.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China.
Up to an estimated 10% of women experience miscarriage in their lifetimes. Embryonic aneuploidy is a leading cause for miscarriage, infertility and congenital defects. Here we identify variants of ELL3, a gene encoding a transcription elongation factor, in couples who experienced consecutive early miscarriages due to embryonic aneuploidy.
View Article and Find Full Text PDFEMBO J
January 2025
Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Elongator is a tRNA-modifying complex that regulates protein translation. Recently, a moonlighting function of Elongator has been identified in regulating the polarization of the microtubule cytoskeleton during asymmetric cell division. Elongator induces symmetry breaking of the anaphase midzone by selectively stabilizing microtubules on one side of the spindle, contributing to the downstream polarized segregation of cell-fate determinants, and therefore to cell fate determination.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Life Science and Medical Bioscience, Laboratory of Cytoskeletal Logistics, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
In mammalian epithelial cells, cytoplasmic microtubules are mainly non-centrosomal, through the functions of the minus-end binding proteins CAMSAP2 and CAMSAP3. When cells enter mitosis, cytoplasmic microtubules are reorganized into the spindle composed of both centrosomal and non-centrosomal microtubules. The function of the CAMSAP proteins upon spindle assembly remains unknown, as these do not exhibit evident localization to spindle microtubules.
View Article and Find Full Text PDFCurr Biol
January 2025
Université Paris Cité, CNRS, Institut Jacques Monod, 75013 Paris, France; Equipe Labellisée LIGUE Contre le Cancer, 75013 Paris, France. Electronic address:
The regulation of mitotic spindle positioning and orientation is central to the morphogenesis of developing embryos and tissues. In many multicellular contexts, cell geometry has been shown to have a major influence on spindle positioning, with spindles that commonly align along the longest cell shape axis. To date, however, we still lack an understanding of how the nature and amplitude of intracellular forces that position, orient, or hold mitotic spindles depend on cell geometry.
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