Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore

Espeut, Julien; Cheerambathur, Dhanya K.; Krenning, Lenno; Oegema, Karen; Desai, Arshad

doi:10.1083/jcb.201111107

Cited by 139 publications

(204 citation statements)

References 37 publications

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“…14 Although Knl1 has also been shown to bind to MT in vitro, 9,13 the major contributor is Hec1/Ndc80, 3,4 since in Caenorhabditis elegans, disruption of Knl1-MT-binding domain did not affect the formation of kMT attachments and chromosome segregation. 13 Crosstalk between the KMN network and SAC signaling…”

Section: The Ndc80 Complexmentioning

confidence: 99%

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How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

Agarwal

Varma

2015

BioArchitecture

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ABSTRACT. Mitosis entails the bona fide segregation of duplicated chromosomes. This process is accomplished by the attachment of kinetochores on chromosomes to microtubules (MTs) of the mitotic spindle. Once the appropriate attachment is achieved, the spindle assembly checkpoint (SAC) that delays the premature onset of anaphase needs to be silenced for the cell to proceed to anaphase and cytokinesis. Therefore, while it is imperative to preserve the SAC when kinetochores are unattached, it is of paramount importance that SAC components are removed post kinetochore microtubule (kMT) attachment. Precise knowledge of how kMT attachments trigger the removal of SAC components from kinetochores or how the checkpoint proteins feedback in to the attachment machinery remains elusive. This review aims to describe the recent advances that provide an insight into the interplay of molecular events that coordinate and regulate the SAC activity in response to kMT attachment during cell division.

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Section: The Ndc80 Complexmentioning

confidence: 99%

“…12 This region also harbors a stretch of 9 basic amino acid residues that display MT-binding activity. 9,13 Importantly, although Knl1 has been shown to directly bind to MTs in vitro, its role in forming force generating end-on kMT attachments has not yet been demonstrated. 12 …”

Section: The Knl1 Complexmentioning

confidence: 99%

How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

Agarwal

Varma

2015

BioArchitecture

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“…Although the Caenorhabditis elegans KMN enhances microtubule binding of the individual components in a cooperative manner, this has not been directly tested with yeast proteins due to the inability to purify recombinant Spc105 and reconstitute yeast KMN . The microtubule binding activity within the nematode KNL1 appears to be important for spindle checkpoint silencing in vivo rather than kinetochore-microtubule coupling activity (Espeut et al 2012). A goal for the future is therefore to determine how the Mis12 and Spc105 subcomplexes contribute to enhancing microtubule-binding activity.…”

Section: Kmnmentioning

confidence: 99%

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

2013

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The propagation of all organisms depends on the accurate and orderly segregation of chromosomes in mitosis and meiosis. Budding yeast has long served as an outstanding model organism to identify the components and underlying mechanisms that regulate chromosome segregation. This review focuses on the kinetochore, the macromolecular protein complex that assembles on centromeric chromatin and maintains persistent load-bearing attachments to the dynamic tips of spindle microtubules. The kinetochore also serves as a regulatory hub for the spindle checkpoint, ensuring that cell cycle progression is coupled to the achievement of proper microtubule-kinetochore attachments. Progress in understanding the composition and overall architecture of the kinetochore, as well as its properties in making and regulating microtubule attachments and the spindle checkpoint, is discussed. TABLE OF CONTENTS Abstract 817Introduction 818

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“…Knl1 binds to MTs (Welburn et al, 2010;Espeut et al, 2012) and has key roles in the kinetochore recruitment of the SAC kinase Bub1 and pseudokinase BubR1 (Kiyomitsu et al, 2007), as well as of the protein phosphatases PP1 (directly) and PP2A (indirectly through BubR1) Suijkerbuijk et al, 2012;Kruse et al, 2013). A number of recent reports have provided important insight into how Knl1 functions as a docking platform that integrates a number of SAC kinase and phosphatase activities.…”

Section: Introductionmentioning

confidence: 99%

“…Knl1 functions as a signaling hub during early mitosis and contributes to the formation of kinetochore-microtubule (MT) attachments (Przewloka and Glover, 2009;Santaguida and Musacchio, 2009). Knl1, the largest subunit of the KMN network, is required for accurate chromosome segregation during mitosis (Desai et al, 2003), and for both activating and inactivating the spindle assembly checkpoint (SAC), a conserved signaling cascade that delays anaphase onset in the presence of unattached or improperly attached chromosomes (Kiyomitsu et al, 2007;Meadows et al, 2011;Rosenberg et al, 2011;Espeut et al, 2012). Defects in Knl1 function have been implicated in genome instability, leukemia, microcephaly and neurological disorders (Kiyomitsu et al, 2007;Kiyomitsu et al, 2011;Yang et al, 2014;Genin et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The dynamic protein Knl1 – a kinetochore rendezvous

Ghongane

Kapanidou

Asghar³

et al. 2014

Journal of Cell Science

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Knl1 (also known as CASC5, UniProt Q8NG31) is an evolutionarily conserved scaffolding protein that is required for proper kinetochore assembly, spindle assembly checkpoint (SAC) function and chromosome congression. A number of recent reports have confirmed the prominence of Knl1 in these processes and provided molecular details and structural features that dictate Knl1 functions in higher organisms. Knl1 recruits SAC components to the kinetochore and is the substrate of certain protein kinases and phosphatases, the interplay of which ensures the exquisite regulation of the aforementioned processes. In this Commentary, we discuss the overall domain organization of Knl1 and the roles of this protein as a versatile docking platform. We present emerging roles of the protein interaction motifs present in Knl1, including the RVSF, SILK, MELT and KI motifs, and their role in the recruitment and regulation of the SAC proteins Bub1, BubR1, Bub3 and Aurora B. Finally, we explore how the regions of low structural complexity that characterize Knl1 are implicated in the cooperative interactions that mediate binding partner recognition and scaffolding activity by Knl1.

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Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore

Abstract: A microtubule-binding site in the extreme N terminus of KNL-1 is dispensable for load-bearing attachments but participates in checkpoint silencing at the kinetochore.

Cited by 139 publications

References 37 publications

How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

How the SAC gets the axe: Integrating kinetochore microtubule attachments with spindle assembly checkpoint signaling

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

The dynamic protein Knl1 – a kinetochore rendezvous

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