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WDR62 is a microcephaly-related, microtubule (MT)-associated protein (MAP) that localizes to the spindle pole and regulates spindle organization, but the underlying mechanisms remain elusive. Here, we show that WDR62 regulates spindle dynamics by recruiting katanin to the spindle pole and further reveal a TPX2-Aurora A-WDR62-katanin axis in cells. By combining cellular and in vitro experiments, we demonstrate that WDR62 shows preference for curved segments of dynamic GDP-MTs, as well as GMPCPP- and paclitaxel-stabilized MTs, suggesting that it recognizes extended MT lattice. Consistent with this property, WDR62 alone is inefficient in recruiting katanin to GDP-MTs, while WDR62 complexed with TPX2/Aurora A can potently promote katanin-mediated severing of GDP-MTs in vitro. In addition, the MT-binding affinity of WDR62 is autoinhibited through JNK phosphorylation-induced intramolecular interaction. We propose that WDR62 is an atypical MAP and functions as an adaptor protein between its recruiting factor TPX2/Aurora A and the effector katanin to orchestrate the regulation of spindle dynamics.
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http://dx.doi.org/10.1083/jcb.202007167 | DOI Listing |
Mitosis in spp., the causative agent of malaria, is fundamentally different from model eukaryotes, proceeding via a bipartite microtubule organising centre (MTOC) and lacking canonical regulators such as Polo and Bub1 kinases. During schizogony, asynchronous nuclear replication produces a multinucleate schizont, while rapid male gametogony generates an octaploid nucleus before gamete formation.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Mammalian female meiosis is uniquely regulated to produce a developmentally competent egg capable of supporting embryogenesis. During meiosis I, homologous chromosomes segregate, with half extruded into the first polar body. The egg then arrests at metaphase II and only resumes meiosis and extrudes the second polar body following fertilization.
View Article and Find Full Text PDFThe parasitic protozoan assembles a bipolar mitotic spindle and undergoes a closed mitosis to segregate its megabase chromosomes and mini-chromosomes through mechanisms that are distinct from its mammalian host. This parasite employs a subset of trypanosome-specific nucleus- and spindle-associated proteins (NuSAPs) to regulate mitosis, but the mechanistic roles of these proteins remain poorly understood. Here, we performed biochemical and molecular characterization of NuSAP1 and analyzed the functional interplay of NuSAP1 with its interacting and proximal proteins.
View Article and Find Full Text PDFStructure
September 2025
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. Electronic address:
Kinesin-8 motors regulate kinetochore-microtubule dynamics and control spindle length and positioning. Certain isoforms achieve this by traversing microtubules, accumulating at plus-ends, and depolymerizing terminal αβ-tubulin subunits. While the kinesin-8 motor domain is well characterized, the tail domain regions are less understood.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
September 2025
Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Tianjin Union Medical Center, the First Affiliated Hospital of Nankai University, Nankai University, Tianjin, China.
The centrosomal protein of 44 kDa (CEP44) is essential for centriole duplication, centrosome cohesion, and spindle integrity. It localizes to the proximal end of centrioles and associates with spindle microtubules. Liquid-liquid phase separation (LLPS) is a process by which biomolecules undergo demixing into distinct liquid-like phases, facilitating the formation of cellular condensates such as the centrosome.
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