A TPR domain–containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B

Nijenhuis, Wilco; Castelmur, Eleonore von; Littler, Dene R.; Marco, Valéria De; Tromer, Eelco C.; Vleugel, Mathijs; Osch, Maria H.J. van; Snel, Berend; Perrakis, Anastassis; Kops, Geert J. P. L.

doi:10.1083/jcb.201210033

Cited by 123 publications

(217 citation statements)

References 65 publications

(117 reference statements)

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“…Consistently, removal of the N-terminal extension (NTE) of Mps1, which is responsible for its localization to kinetochores (designated as Mps1 KD-Δ60 ), reduced the level of Mps1 at kinetochores but did not affect chromosome alignment ( Fig. 4 A and B) (21). Similarly, the previously reported phospho-mimicking Mps1 mutant in Mps1 KD (designated as Mps1 KD-8D ) also induced a slight chromosome alignment defect because of its weaker localization on kinetochores ( Mps1 inhibitors is caused mainly by the elevated localization of an inactive form of Mps1 in the kinetochore.…”

Section: Inactive Mps1 Accumulates Abnormally At Kinetochores Leadinmentioning

confidence: 56%

“…Although the molecular mechanism remains unclear, Mps1 is required to recruit Mad1 and Mad2 to unattached kinetochores, supporting its essential role in SAC activity (15)(16)(17)(18). It also is clear that aurora B kinase activity and the outer-layer kinetochore protein nuclear division cycle 80 (Ndc80)/Hec1 are required for Mps1 localization to kinetochores, as evidenced by recent work, including ours (17,(19)(20)(21)(22)(23)(24). How Mps1 activates the SAC is now becoming clear.…”

mentioning

confidence: 81%

“…Second, although two Mps1 mutants with a disrupted TPR domain (a domain shown to be responsible for the kinetochore localization of Mps1 WT ) fail to localize to kinetochores, inhibition of their kinase activity with reversine restores their normal kinetochore localization (48). Third, Mps1 mutants lacking the entire TPR domain localize to kinetochore in the presence of reversine (21). Therefore, it is likely that Mps1 localizes to kinetochores independently of its TPR domain.…”

Section: Inactive and Active Mps1 Kinases Exhibit Distinctly Differenmentioning

confidence: 99%

“…One candidate region could be the NTE (amino acids 1-61) of Mps1, because it is important for targeting Mps1 to kinetochores (21). Therefore we tested the kinetochore localization of GFPtagged Mps1 .…”

Section: Inactive and Active Mps1 Kinases Exhibit Distinctly Differenmentioning

confidence: 99%

“…How then does the accumulated inactive Mps1 at kinetochores affect chromosome alignment? Because the Hec1 MT-binding domain also is required for recruiting Mps1 to kinetochores (21,23), it is likely that the Hec1-MT binding and Hec1-Mps1 binding are mutually exclusive. In support of this view, our study showed that the kinetochore localization of inactive Mps1, but not active Mps1, prevented the establishment of stable kinetochore-MT attachments.…”

Section: Mis12cmentioning

confidence: 99%

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Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dou

Liu

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.Mps1 kinase | spindle assembly checkpoint | chromosome alignment | kinetochore-microtubule attachment | reversine

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Section: Inactive Mps1 Accumulates Abnormally At Kinetochores Leadinmentioning

confidence: 56%

mentioning

confidence: 81%

Section: Inactive and Active Mps1 Kinases Exhibit Distinctly Differenmentioning

confidence: 99%

Section: Inactive and Active Mps1 Kinases Exhibit Distinctly Differenmentioning

confidence: 99%

Section: Mis12cmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dou

Liu

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Orchestration of the spindle assembly checkpoint by CDK1‐cyclin B1

2019

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In mitosis, the spindle assembly checkpoint (SAC) monitors the formation of microtubule‐kinetochore attachments during capture of chromosomes by the mitotic spindle. Spindle assembly is complete once there are no longer any unattached kinetochores. Here, we will discuss the mechanism and key components of spindle checkpoint signalling. Unattached kinetochores bind the principal spindle checkpoint kinase monopolar spindle 1 (MPS1). MPS1 triggers the recruitment of other spindle checkpoint proteins and the formation of a soluble inhibitor of anaphase, thus preventing exit from mitosis. On microtubule attachment, kinetochores become checkpoint silent due to the actions of PP2A‐B56 and PP1. This SAC responsive period has to be coordinated with mitotic spindle formation to ensure timely mitotic exit and accurate chromosome segregation. We focus on the molecular mechanisms by which the SAC permissive state is created, describing a central role for CDK1‐cyclin B1 and its counteracting phosphatase PP2A‐B55. Furthermore, we discuss how CDK1‐cyclin B1, through its interaction with MAD1, acts as an integral component of the SAC, and actively orchestrates checkpoint signalling and thus contributes to the faithful execution of mitosis.

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Inferring the Evolutionary History of Your Favorite Protein: A Guide for Molecular Biologists

et al. 2019

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Comparative genomics has proven a fruitful approach to acquire many functional and evolutionary insights into core cellular processes. Here it is argued that in order to perform accurate and interesting comparative genomics, one first and foremost has to be able to recognize, postulate, and revise different evolutionary scenarios. After all, these studies lack a simple protocol, due to different proteins having different evolutionary dynamics and demanding different approaches. The authors here discuss this challenge from a practical (what are the observations?) and conceptual (how do these indicate a specific evolutionary scenario?) viewpoint, with the aim to guide investigators who want to analyze the evolution of their protein(s) of interest. By sharing how the authors draft, test, and update such a scenario and how it directs their investigations, the authors hope to illuminate how to execute molecular evolution studies and how to interpret them. Also see the video abstract here https://youtu.be/VCt3l2pbdbQ.

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A TPR domain–containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B

Abstract: The kinetochore localization of MPS1 is necessary for mitotic checkpoint activity and requires the microtubule-binding domain of HEC1 and the Aurora B–dependent regulation of the TPR domain.

Cited by 123 publications

References 65 publications

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Orchestration of the spindle assembly checkpoint by CDK1‐cyclin B1

Inferring the Evolutionary History of Your Favorite Protein: A Guide for Molecular Biologists

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