scholarly journals Knl1 participates in spindle assembly checkpoint signaling in maize

2021 ◽  
Vol 118 (20) ◽  
pp. e2022357118
Author(s):  
Handong Su ◽  
Yang Liu ◽  
Chunhui Wang ◽  
Yalin Liu ◽  
Chao Feng ◽  
...  
Keyword(s):  
Cell Division ◽  
Evolutionary History ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Helical Conformation ◽  
Evolutionary Patterns ◽  
Checkpoint Signaling ◽  
Microtubule Attachment ◽  
Tpr Domain

The Knl1-Mis12-Ndc80 (KMN) network is an essential component of the kinetochore–microtubule attachment interface, which is required for genomic stability in eukaryotes. However, little is known about plant Knl1 proteins because of their complex evolutionary history. Here, we cloned the Knl1 homolog from maize (Zea mays) and confirmed it as a constitutive central kinetochore component. Functional assays demonstrated their conserved role in chromosomal congression and segregation during nuclear division, thus causing defective cell division during kernel development when Knl1 transcript was depleted. A 145 aa region in the middle of maize Knl1, that did not involve the MELT repeats, was associated with the interaction of spindle assembly checkpoint (SAC) components Bub1/Mad3 family proteins 1 and 2 (Bmf1/2) but not with the Bmf3 protein. They may form a helical conformation with a hydrophobic interface with the TPR domain of Bmf1/2, which is similar to that of vertebrates. However, this region detected in monocots shows extensive divergence in eudicots, suggesting that distinct modes of the SAC to kinetochore connection are present within plant lineages. These findings elucidate the conserved role of the KMN network in cell division and a striking dynamic of evolutionary patterns in the SAC signaling and kinetochore network.

scholarly journals Interactions between N-Terminal Modules in MPS1 Enable Spindle Checkpoint Silencing

2018 ◽  
Author(s):  
Spyridon T. Pachis ◽  
Yoshitaka Hiruma ◽  
Anastassis Perrakis ◽  
Geert J.P.L. Kops
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Intramolecular Interactions ◽  
Mitotic Progression ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
Regulatory Input ◽  
Tpr Domain

ABSTRACTFaithful chromosome segregation relies on the ability of the spindle assembly checkpoint (SAC) to delay anaphase onset until all chromosomes are attached to the mitotic spindle via their kinetochores. MPS1 kinase is recruited to unattached kinetochores to initiate SAC signaling, and is removed from kinetochores once stable microtubule attachments have been formed to allow normal mitotic progression. Here we show that a helical fragment within the kinetochore-targeting NTE module of MPS1 is required for interactions with kinetochores, and also forms intramolecular interactions with its adjacent TPR domain. Bypassing this NTE-TPR interaction results in high MPS1 levels at kinetochores due to loss of regulatory input into MPS1 localization, ineffecient MPS1 delocalization from kinetochores upon microtubule attachment, and SAC silencing defects. These results show that SAC responsiveness to attachments relies on regulated intramolecular interactions in MPS1 and highlight the sensitivity of mitosis to perturbations in the dynamics of the MSP1-NDC80-C interactions.

scholarly journals Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation

2019 ◽  
Vol 218 (12) ◽  
pp. 3926-3942 ◽  
Author(s):  
Babhrubahan Roy ◽  
Vikash Verma ◽  
Janice Sim ◽  
Adrienne Fontan ◽  
Ajit P. Joglekar
Keyword(s):  
Cell Division ◽  
Error Correction ◽  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Spindle Assembly Checkpoint ◽  
Spindle Checkpoint ◽  
Spindle Assembly ◽  
Protein Phosphatase 1 ◽  
Microtubule Attachment ◽  
Error Correction Mechanism

Accurate chromosome segregation during cell division requires the spindle assembly checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect kinetochore–microtubule attachments. While the SAC and error correction are both regulated by protein phosphatase 1 (PP1), which silences the SAC and stabilizes kinetochore–microtubule attachments, how these distinct PP1 functions are coordinated remains unclear. Here, we investigate the contribution of PP1, docked on its conserved kinetochore receptor Spc105/Knl1, to SAC silencing and attachment regulation. We find that Spc105-bound PP1 is critical for SAC silencing but dispensable for error correction; in fact, reduced PP1 docking on Spc105 improved chromosome segregation and viability of mutant/stressed states. We additionally show that artificially recruiting PP1 to Spc105/Knl1 before, but not after, chromosome biorientation interfered with error correction. These observations lead us to propose that recruitment of PP1 to Spc105/Knl1 is carefully regulated to ensure that chromosome biorientation precedes SAC silencing, thereby ensuring accurate chromosome segregation.

scholarly journals Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment

2019 ◽  
Vol 30 (9) ◽  
pp. 1060-1068 ◽  
Author(s):  
Hongdan Yang ◽  
Fengxia Zhang ◽  
Ching-Jung Huang ◽  
Jun Liao ◽  
Ying Han ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Underlying Mechanism ◽  
Genome Maintenance ◽  
Microtubule Attachment ◽  
Downstream Effectors ◽  
Chromosome Alignment ◽  
Assembly Factor ◽  
Spindle Microtubules

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore–microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore–microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood. Here, we show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules. Thus, our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance.

scholarly journals Spindle assembly checkpoint proteins are positioned close to core microtubule attachment sites at kinetochores

2013 ◽  
Vol 202 (5) ◽  
pp. 735-746 ◽  
Author(s):  
Dileep Varma ◽  
Xiaohu Wan ◽  
Dhanya Cheerambathur ◽  
Reto Gassmann ◽  
Aussie Suzuki ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Attachment Site ◽  
Spindle Assembly ◽  
Nanometer Scale ◽  
Outer Plate ◽  
Checkpoint Signaling ◽  
Checkpoint Proteins ◽  
Microtubule Attachment ◽  
C Terminus ◽  
Attachment Sites

Spindle assembly checkpoint proteins have been thought to reside in the peripheral corona region of the kinetochore, distal to microtubule attachment sites at the outer plate. However, recent biochemical evidence indicates that checkpoint proteins are closely linked to the core kinetochore microtubule attachment site comprised of the Knl1–Mis12–Ndc80 (KMN) complexes/KMN network. In this paper, we show that the Knl1–Zwint1 complex is required to recruit the Rod–Zwilch–Zw10 (RZZ) and Mad1–Mad2 complexes to the outer kinetochore. Consistent with this, nanometer-scale mapping indicates that RZZ, Mad1–Mad2, and the C terminus of the dynein recruitment factor Spindly are closely juxtaposed with the KMN network in metaphase cells when their dissociation is blocked and the checkpoint is active. In contrast, the N terminus of Spindly is ∼75 nm outside the calponin homology domain of the Ndc80 complex. These results reveal how checkpoint proteins are integrated within the substructure of the kinetochore and will aid in understanding the coordination of microtubule attachment and checkpoint signaling during chromosome segregation.

FANCA Controls Mitotic Phosphosignaling Networks To Ensure Genome Stability During Cell Division

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 801-801
Author(s):  
Rikki Enzor ◽  
Zahi Abdul Sater ◽  
Donna Cerabona ◽  
Zejin Sun ◽  
Su-jung Park ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Fanconi Anemia ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Signaling Network ◽  
Mitotic Apparatus ◽  
Risk Of Cancer

Abstract Fanconi anemia (FA) is a heterogenous genome instability syndrome with a high risk of cancer. The FA proteins are essential for interphase DNA damage repair. However, it is incompletely understood why FA-deficient cells also develop gross aneuploidy and multinucleation, which are symptoms of error-prone chromosome segregation. Emerging evidence indicates that the FA signaling network functions as a guardian of the genome throughout the cell cycle, including chromosome segregation during mitosis. However, the mechanistic aspects of the critical role of the FA signaling in mitosis remain poorly understood. We have recently shown that the FA signaling network localizes to the mitotic apparatus to control the spindle assembly checkpoint and centrosome maintenance (J Clin Invest 2013, in press). The spindle assembly checkpoint (SAC) is a complex tumor suppressor signaling network that prevents premature separation of sister chromatids by delaying the metaphase-to-anaphase transition until all the kinetochores are properly attached to the mitotic spindle. Since weakened SAC promotes stochastic chromosome segregation, mutagenesis and cancer, these findings shed new light on the role of FA signaling in maintenance of genomic stability. We found the subcellular localization of FA proteins to the mitotic apparatus is spatiotemporally regulated as cells divide. Our new data revealed the pathways connecting the FANCA protein with canonical mitotic phosphosignaling networks. We have employed unbiased kinome-wide phospho-mass spectrometry to compare the landscape of abnormalities of mitotic signaling pathways in primary FANCA-/- patient cells and gene-corrected isogenic cells. These experiments led us to identify and quantify a wide range of phosphorylation abnormalities of multiple FANCA-dependent centrosome-, kinetochore- and chromosome-associated regulators of mitosis. Our data illuminated the role for FA signaling in three critical stages of cell division: (1) the spindle assembly checkpoint, (2) anaphase and (3) cytokinesis. Thus, we employed live phase-contrast imaging of primary FANCA-/- patient cells in comparison to gene-corrected cells to separately quantify aberrations in (1) chromosome congression and metaphase-anaphase transition (SAC malfunction), (2) execution of anaphase and (3) completion of cytokinesis. Our findings further our understanding of human cell cycle control and provide new insights into the origins of genomic instability in Fanconi anemia by establishing mechanistic connection between the FANCA protein and key mitotic signaling networks. The identification of cell division pathways regulated by FANCA has implications for future targeted drug development in Fanconi anemia and FA-deficient malignancies in the general population. Disclosures: No relevant conflicts of interest to declare.

Spindle Assembly Checkpoint Protein Dynamics and Roles in Plant Cell Division

2011 ◽  
pp. 142-153
Author(s):  
Marie-Cécile Caillaud ◽  
Laetitia Paganelli ◽  
Philippe Lecomte ◽  
Laurent Deslandes ◽  
Michaël Quentin ◽  
...  
Keyword(s):  
Cell Division ◽  
Protein Dynamics ◽  
Plant Cell ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Checkpoint Protein ◽  
Plant Cell Division ◽  
Spindle Assembly Checkpoint Protein

scholarly journals Author response: Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling

2013 ◽  
Author(s):  
Ivana Primorac ◽  
John R Weir ◽  
Elena Chiroli ◽  
Fridolin Gross ◽  
Ingrid Hoffmann ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Author Response ◽  
Checkpoint Signaling

scholarly journals Regulation of the meiotic divisions of mammalian oocytes and eggs

2018 ◽  
Vol 46 (4) ◽  
pp. 797-806 ◽  
Author(s):  
Jessica R. Sanders ◽  
Keith T. Jones
Keyword(s):  
Cell Division ◽  
Luteinizing Hormone ◽  
Spindle Assembly Checkpoint ◽  
Asymmetric Cell Division ◽  
Homologous Chromosomes ◽  
Mammalian Oocyte ◽  
Cellular Events ◽  
The Hours ◽  
Meiosis I

Initiated by luteinizing hormone and finalized by the fertilizing sperm, the mammalian oocyte completes its two meiotic divisions. The first division occurs in the mature Graafian follicle during the hours preceding ovulation and culminates in an extreme asymmetric cell division and the segregation of the two pairs of homologous chromosomes. The newly created mature egg rearrests at metaphase of the second meiotic division prior to ovulation and only completes meiosis following a Ca2+ signal initiated by the sperm at gamete fusion. Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. In meiosis II, we examine how the egg achieves its arrest and how the fertilization Ca2+ signal allows the initiation of embryo development.

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