Correct function of the mitotic spindle requires balanced interplay of kinetochore and astral microtubules that mediate chromosome segregation and spindle positioning, respectively. Errors therein can cause severe defects ranging from aneuploidy to developmental disorders. Here, we describe a protein degradation pathway that functionally links astral microtubules to kinetochores via regulation of a microtubule-associated factor. We show that the yeast spindle positioning protein Kar9 localizes not only to astral but also to kinetochore microtubules, where it becomes targeted for proteasomal degradation by the SUMO-targeted ubiquitin ligases (STUbLs) Slx5-Slx8. Intriguingly, this process does not depend on preceding sumoylation of Kar9 but rather requires SUMO-dependent recruitment of STUbLs to kinetochores. Failure to degrade Kar9 leads to defects in both chromosome segregation and spindle positioning. We propose that kinetochores serve as platforms to recruit STUbLs in a SUMO-dependent manner in order to ensure correct spindle function by regulating levels of microtubule-associated proteins.
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http://dx.doi.org/10.1016/j.devcel.2016.01.011 | DOI Listing |
Aim: Within the in vitro fertilization (IVF) process, to evaluate the possibility of using the state of the meiotic spindle of oocytes as an indicator of maturity in order to optimize the timing of vitrification.
Patients And Methods: In the presented report, the cause of couple infertility was a combination of a 38-year-old female and 43-year-old male with azoospermia, which was an indication for oocyte vitrification. Oocyte polar bodies and optically birefringent meiotic spindles were visualized by polarized light microscopy and their states and relative positions were used as indicators of oocyte maturation, i.
Biol Open
December 2024
Institut Curie, Université PSL, CNRS UMR3348, 91400 Orsay, France.
The SUMO-targeted ubiquitin ligase (STUbL) family is involved in multiple cellular processes via a wide range of mechanisms to maintain genome stability. One of the evolutionarily conserved functions of STUbL is to promote changes in the nuclear positioning of DNA lesions, targeting them to the nuclear periphery. In Schizossacharomyces pombe, the STUbL Slx8 is a regulator of SUMOylated proteins and promotes replication stress tolerance by counteracting the toxicity of SUMO conjugates.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan.
Female infertility is a significant healthcare burden that is frequently encountered among couples globally. While environmental factors, comorbidities, and lifestyle determine reproductive health, certain genetic variants in key reproductive genes can potentially cause unsuccessful pregnancies. Such crucial proteins have been identified within the subcortical maternal complex (SCMC) and play an integral role in the early stages of embryogenesis before embryo implantation.
View Article and Find Full Text PDFNat Commun
January 2025
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Heidelberg, Germany.
The γ-tubulin ring complex (γ-TuRC) is a structural template for controlled nucleation of microtubules from α/β-tubulin heterodimers. At the cytoplasmic side of the yeast spindle pole body, the CM1-containing receptor protein Spc72 promotes γ-TuRC assembly from seven γ-tubulin small complexes (γ-TuSCs) and recruits the microtubule polymerase Stu2, yet their molecular interplay remains unclear. Here, we determine the cryo-EM structure of the Candida albicans cytoplasmic nucleation unit at 3.
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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