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In a wide range of eukaryotes, chromosome segregation occurs through anaphase A, in which chromosomes move toward stationary spindle poles, anaphase B, in which chromosomes move at the same velocity as outwardly moving spindle poles, or both. In contrast, Caenorhabditis elegans female meiotic spindles initially shorten in the pole-to-pole axis such that spindle poles contact the outer kinetochore before the start of anaphase chromosome separation. Once the spindle pole-to-kinetochore contact has been made, the homologues of a 4-μm-long bivalent begin to separate. The spindle shortens an additional 0.5 μm until the chromosomes are embedded in the spindle poles. Chromosomes then separate at the same velocity as the spindle poles in an anaphase B-like movement. We conclude that the majority of meiotic chromosome movement is caused by shortening of the spindle to bring poles in contact with the chromosomes, followed by separation of chromosome-bound poles by outward sliding., (© 2016 McNally et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

The conserved Bub1/Bub3 complex is recruited to the kinetochore region of mitotic chromosomes, where it initiates spindle checkpoint signaling and promotes chromosome alignment. Here we show that, in contrast to the expectation for a checkpoint pathway component, the BUB-1/BUB-3 complex promotes timely anaphase onset in Caenorhabditis elegans embryos. This activity of BUB-1/BUB-3 was independent of spindle checkpoint signaling but required kinetochore localization. BUB-1/BUB-3 inhibition equivalently delayed separase activation and other events occurring during mitotic exit. The anaphase promotion function required BUB-1's kinase domain, but not its kinase activity, and this function was independent of the role of BUB-1/BUB-3 in chromosome alignment. These results reveal an unexpected role for the BUB-1/BUB-3 complex in promoting anaphase onset that is distinct from its well-studied functions in checkpoint signaling and chromosome alignment, and suggest a new mechanism contributing to the coordination of the metaphase-to-anaphase transition.

The accurate distribution of the replicated genome during cell division is essential for cell survival and healthy organismal development. Errors in this process have catastrophic consequences, such as birth defects and aneuploidy, a hallmark of cancer cells. PLK1 is one of the master kinases in mitosis and has multiple functions, including mitotic entry, chromosome segregation, spindle assembly checkpoint, and cytokinesis. To dissect the role of PLK1 in mitosis, it is important to understand how PLK1 localizes in the specific region in cells. PLK1 localizes at the kinetochore and is essential in spindle assembly checkpoint and chromosome segregation. However, how PLK1 localizes at the kinetochore remains elusive. Here, we review the recent literature on the kinetochore recruitment mechanisms of PLK1 and its roles in spindle assembly checkpoint and attachment between kinetochores and spindle microtubules. Together, this review provides an overview of how the local distribution of PLK1 could regulate major pathways in mitosis. [ABSTRACT FROM AUTHOR]

Accurate chromosome segregation is required for cell survival and organismal development. During mitosis, the spindle assembly checkpoint acts as a safeguard to maintain the high fidelity of mitotic chromosome segregation by monitoring the attachment of kinetochores to the mitotic spindle. Bub1 is a conserved kinase critical for the spindle assembly checkpoint. Bub1 also facilitates chromosome alignment and contributes to the regulation of mitotic duration. Here, focusing on the spindle assembly checkpoint and on chromosome alignment, we summarize the primary literature on Bub1, discussing its structure and functional domains, as well its regulation and roles in mitosis. In addition, we discuss recent evidence for roles of Bub1 beyond mitosis regulation in TGFβ signaling and telomere replication. Finally, we discuss the involvement of Bub1 in human diseases, especially in cancer, and the potential of using Bub1 as a drug target for therapeutic applications. [ABSTRACT FROM AUTHOR]

A critical structure poised to coordinate chromosome segregation with division plane specification is the central spindle that forms between separating chromosomes after anaphase onset. The central spindle acts as a signalling centre that concentrates proteins essential for division plane specification and contractile ring constriction. However, the molecular mechanisms that control the initial stages of central spindle assembly remain elusive. Using Caenorhabditis elegans zygotes, we found that the microtubule-bundling protein SPD-1PRC1 and the motor ZEN-4MKLP-1 are required for proper central spindle structure during its elongation. In contrast, we found that the kinetochore controls the initiation of central spindle assembly. Specifically, central spindle microtubule assembly is dependent on kinetochore recruitment of the scaffold protein KNL-1, as well as downstream partners BUB-1, HCP-1/2CENP-F and CLS-2CLASP; and is negatively regulated by kinetochore-associated protein phosphatase 1 activity. This in turn promotes central spindle localization of CLS-2CLASP and initial central spindle microtubule assembly through its microtubule polymerase activity. Together, our results reveal an unexpected role for a conserved kinetochore protein network in coupling two critical events of cell division: chromosome segregation and cytokinesis. [ABSTRACT FROM AUTHOR]

During mitosis, chromosomes assemble kinetochores to dynamically couple with spindle microtubules. 1,2 Kinetochores also function as signaling hubs directing mitotic progression by recruiting and controlling the fate of the anaphase promoting complex/cyclosome (APC/C) activator CDC-20. 3,4,5 Kinetochores either incorporate CDC-20 into checkpoint complexes that inhibit the APC/C or dephosphorylate CDC-20, which allows it to interact with and activate the APC/C. 4,6 The importance of these two CDC-20 fates likely depends on the biological context. In human somatic cells, the major mechanism controlling mitotic progression is the spindle checkpoint. By contrast, progression through mitosis during the cell cycles of early embryos is largely checkpoint independent. 7,8,9,10 Here, we first show that CDC-20 phosphoregulation controls mitotic duration in the C. elegans embryo and defines a checkpoint-independent temporal mitotic optimum for robust embryogenesis. CDC-20 phosphoregulation occurs at kinetochores and in the cytosol. At kinetochores, the flux of CDC-20 for local dephosphorylation requires an ABBA motif on BUB-1 that directly interfaces with the structured WD40 domain of CDC-20. 6,11,12,13 We next show that a conserved "STP" motif in BUB-1 that docks the mitotic kinase PLK-1 14 is necessary for CDC-20 kinetochore recruitment and timely mitotic progression. The kinase activity of PLK-1 is required for CDC-20 to localize to kinetochores and phosphorylates the CDC-20-binding ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction and mitotic progression. Thus, the BUB-1-bound pool of PLK-1 ensures timely mitosis during embryonic cell cycles by promoting CDC-20 recruitment to the vicinity of kinetochore-localized phosphatase activity. • An optimal mitotic duration is important for robust C. elegans embryogenesis • Activation of CDC-20 at kinetochores controls embryonic mitotic duration • Kinetochore recruitment of CDC-20 by BUB-1 requires BUB-1-bound PLK-1 • Phosphorylation of BUB-1 by PLK-1 enhances binding and recruitment of CDC-20 Houston et al. show that an optimal mitotic duration set independently of the spindle checkpoint by phosphoregulation of CDC-20 ensures robust C. elegans embryogenesis. They also show that CDC-20 flux through kinetochores, which is important for its activation, requires BUB-1-bound PLK-1, whose kinase activity enhances CDC-20 binding to BUB-1. [ABSTRACT FROM AUTHOR]