scholarly journals Leaving no-one behind: how CENP-E facilitates chromosome alignment

2020 ◽  
Vol 64 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Benjamin Craske ◽  
Julie P.I. Welburn
Keyword(s):  
Motor Activity ◽  
Recent Work ◽  
Transport Mechanism ◽  
Genomic Stability ◽  
Mitotic Progression ◽  
Kinesin Motor ◽  
Independent Manner ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Microtubule Motor

Abstract Chromosome alignment and biorientation is essential for mitotic progression and genomic stability. Most chromosomes align at the spindle equator in a motor-independent manner. However, a subset of polar kinetochores fail to bi-orient and require a microtubule motor-based transport mechanism to move to the cell equator. Centromere Protein E (CENP-E/KIF10) is a kinesin motor from the Kinesin-7 family, which localizes to unattached kinetochores during mitosis and utilizes plus-end directed microtubule motility to slide mono-oriented chromosomes to the spindle equator. Recent work has revealed how CENP-E cooperates with chromokinesins and dynein to mediate chromosome congression and highlighted its role at aligned chromosomes. Additionally, we have gained new mechanistic insights into the targeting and regulation of CENP-E motor activity at the kinetochore. Here, we will review the function of CENP-E in chromosome congression, the pathways that contribute to CENP-E loading at the kinetochore, and how CENP-E activity is regulated during mitosis.

scholarly journals CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tether

2008 ◽  
Vol 181 (3) ◽  
pp. 411-419 ◽  
Author(s):  
Yumi Kim ◽  
John E. Heuser ◽  
Clare M. Waterman ◽  
Don W. Cleveland
Keyword(s):  
Motor Activity ◽  
Single Molecule ◽  
Coiled Coil ◽  
Full Length ◽  
Direct Visualization ◽  
Chromosome Missegregation ◽  
Microtubule Attachment ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Spindle Microtubules

The mitotic kinesin centromere protein E (CENP-E) is an essential kinetochore component that directly contributes to the capture and stabilization of spindle microtubules by kinetochores. Although reduction in CENP-E leads to high rates of whole chromosome missegregation, neither its properties as a microtubule-dependent motor nor how it contributes to the dynamic linkage between kinetochores and microtubules is known. Using single-molecule assays, we demonstrate that CENP-E is a very slow, highly processive motor that maintains microtubule attachment for long periods. Direct visualization of full-length Xenopus laevis CENP-E reveals a highly flexible 230-nm coiled coil separating its kinetochore-binding and motor domains. We also show that full-length CENP-E is a slow plus end–directed motor whose activity is essential for metaphase chromosome alignment. We propose that the highly processive microtubule-dependent motor activity of CENP-E serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules.

scholarly journals RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

2009 ◽  
Vol 20 (1) ◽  
pp. 410-418 ◽  
Author(s):  
Ulf R. Klein ◽  
Markus Haindl ◽  
Erich A. Nigg ◽  
Stefan Muller
Keyword(s):  
Mammalian Cells ◽  
Spindle Assembly Checkpoint ◽  
Critical Role ◽  
Specific Interaction ◽  
Regulatory Function ◽  
Mitotic Progression ◽  
Chromosome Congression ◽  
Chromosomal Passenger

The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation–deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway.

scholarly journals Identification of an Axonal Kinesin-3 Motor for Fast Anterograde Vesicle Transport that Facilitates Retrograde Transport of Neuropeptides

2008 ◽  
Vol 19 (1) ◽  
pp. 274-283 ◽  
Author(s):  
Rosemarie V. Barkus ◽  
Olga Klyachko ◽  
Dai Horiuchi ◽  
Barry J. Dickson ◽  
William M. Saxton
Keyword(s):  
Transport Mechanism ◽  
Fluorescent Protein ◽  
Retrograde Transport ◽  
Major Contributor ◽  
Anterograde Transport ◽  
Microtubule Motor ◽  
Fast Transport ◽  
Green Fluorescent ◽  
Neuronal Functions ◽  
Axonal Swellings

A screen for genes required in Drosophila eye development identified an UNC-104/Kif1 related kinesin-3 microtubule motor. Analysis of mutants suggested that Drosophila Unc-104 has neuronal functions that are distinct from those of the classic anterograde axonal motor, kinesin-1. In particular, unc-104 mutations did not cause the distal paralysis and focal axonal swellings characteristic of kinesin-1 (Khc) mutations. However, like Khc mutations, unc-104 mutations caused motoneuron terminal atrophy. The distributions and transport behaviors of green fluorescent protein-tagged organelles in motor axons indicate that Unc-104 is a major contributor to the anterograde fast transport of neuropeptide-filled vesicles, that it also contributes to anterograde transport of synaptotagmin-bearing vesicles, and that it contributes little or nothing to anterograde transport of mitochondria, which are transported primarily by Khc. Remarkably, unc-104 mutations inhibited retrograde runs by neurosecretory vesicles but not by the other two organelles. This suggests that Unc-104, a member of an anterograde kinesin subfamily, contributes to an organelle-specific dynein-driven retrograde transport mechanism.

scholarly journals Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sabrina F Mansilla ◽  
Agustina P Bertolin ◽  
Valérie Bergoglio ◽  
Marie-Jeanne Pillaire ◽  
Marina A González Besteiro ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Genomic Stability ◽  
S Phase ◽  
Fragile Sites ◽  
Dna Lesions ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Independent Manner ◽  
Genomic Regions

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis.

scholarly journals Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

2021 ◽  
Vol 118 (34) ◽  
pp. e2108145118
Author(s):  
Anja Bufe ◽  
Ana García del Arco ◽  
Magdalena Hennecke ◽  
Anchel de Jaime-Soguero ◽  
Matthias Ostermaier ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Wnt Signaling ◽  
Pluripotent Stem Cells ◽  
Target Genes ◽  
Genome Maintenance ◽  
Spindle Poles ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Canonical Wnt

Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating β-catenin target genes. Recent evidence showed that β-catenin–independent Wnt signaling is also required for faithful execution of mitosis. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.

scholarly journals The association of Plk1 with the astrin–kinastrin complex promotes formation and maintenance of a metaphase plate

2020 ◽  
Vol 134 (1) ◽  
pp. jcs251025
Author(s):  
Zoë Geraghty ◽  
Christina Barnard ◽  
Pelin Uluocak ◽  
Ulrike Gruneberg
Keyword(s):  
Molecular Mechanisms ◽  
Metaphase Plate ◽  
Direct Interaction ◽  
Mitotic Chromosomes ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Mitotic Kinase ◽  
Spindle Poles ◽  
Chromosome Congression ◽  
Chromosome Alignment

ABSTRACTErrors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin–kinastrin (astrin is also known as SPAG5 and kinastrin as SKAP) complex, also containing DYNLL1 and MYCBP, is a spindle and kinetochore protein complex with important roles in bipolar spindle formation, chromosome alignment and microtubule–kinetochore attachment. However, the molecular mechanisms by which astrin–kinastrin fulfils these diverse roles are not fully understood. Here, we characterise a direct interaction between astrin and the mitotic kinase Plk1. We identify the Plk1-binding site on astrin as well as four Plk1 phosphorylation sites on astrin. Regulation of astrin by Plk1 is dispensable for bipolar spindle formation and bulk chromosome congression, but promotes stable microtubule–kinetochore attachments and metaphase plate maintenance. It is known that Plk1 activity is required for effective microtubule–kinetochore attachment formation, and we suggest that astrin phosphorylation by Plk1 contributes to this process.

scholarly journals BicaudalD Actively Regulates Microtubule Motor Activity in Lipid Droplet Transport

PLoS ONE ◽  
2008 ◽  
Vol 3 (11) ◽  
pp. e3763 ◽  
Author(s):  
Kristoffer S. Larsen ◽  
Jing Xu ◽  
Silvia Cermelli ◽  
Zhanyong Shu ◽  
Steven P. Gross
Keyword(s):  
Motor Activity ◽  
Lipid Droplet ◽  
Droplet Transport ◽  
Microtubule Motor

scholarly journals Phosphotransferases Associated with the Regulation of Kinesin Motor Activity

1997 ◽  
Vol 272 (36) ◽  
pp. 22929-22933 ◽  
Author(s):  
Lisa Lindesmith ◽  
James M. McIlvain ◽  
Yair Argon ◽  
Michael P. Sheetz
Keyword(s):  
Motor Activity ◽  
Kinesin Motor

scholarly journals KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC

2010 ◽  
Vol 190 (3) ◽  
pp. 443-460 ◽  
Author(s):  
Fanny Jaulin ◽  
Geri Kreitzer
Keyword(s):  
Motor Activity ◽  
Adenomatous Polyposis Coli ◽  
Three Dimensional ◽  
Epithelial Morphogenesis ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Kinesin Motor ◽  
Central Lumen ◽  
Selective Stabilization ◽  
Epithelial Cysts

Epithelial polarization is associated with selective stabilization and reorganization of microtubule (MT) arrays. However, upstream events and downstream consequences of MT stabilization during epithelial morphogenesis are still unclear. We show that the anterograde kinesin KIF17 localizes to MT plus ends, stabilizes MTs, and affects epithelial architecture. Targeting of KIF17 to plus ends of growing MTs requires kinesin motor activity and interaction with EB1. In turn, KIF17 participates in localizing adenomatous polyposis coli (APC) to the plus ends of a subset of MTs. We found that KIF17 affects MT dynamics, polymerization rates, and MT plus end stabilization to generate posttranslationally acetylated MTs. Depletion of KIF17 from cells growing in three-dimensional matrices results in aberrant epithelial cysts that fail to generate a single central lumen and to polarize apical markers. These findings implicate KIF17 in MT stabilization events that contribute to epithelial polarization and morphogenesis.

scholarly journals Coordination of Chromosome Alignment and Mitotic Progression Chromosome-Based Ran Signal

Cell Cycle ◽  
2007 ◽  
Vol 6 (15) ◽  
pp. 1886-1895 ◽  
Author(s):  
Hoi Y. Li ◽  
Win Pin Ng ◽  
Wong Chi Hang ◽  
Pablo A. Iglesias ◽  
Yixian Zheng
Keyword(s):  
Mitotic Progression ◽  
Chromosome Alignment
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