Mechanism of Ska Recruitment by Ndc80 Complexes to Kinetochores

Janczyk, Paweł; Skorupka, Katarzyna; Tooley, John G.; Matson, Daniel R.; Kestner, Cortney A.; West, Thomas; Pornillos, Owen; Stukenberg, P. Todd

doi:10.1016/j.devcel.2017.04.020

Cited by 51 publications

(67 citation statements)

References 54 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, although the Ska1 MTBD is necessary and sufficient for Ska1 complex microtubule binding and spindle localization [2], we note that recent work has also suggested a contribution to microtubule interactions from Ska3 [28]. Ultimately, these activities must be regulated [13, 29, 30] and integrated with other players at the kinetochore, including the Ndc80 complex [2, 31, 32], to ensure faithful chromosome segregation during every cell division.…”

Section: Resultsmentioning

confidence: 99%

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

et al. 2017

View full text Add to dashboard Cite

Summary The macromolecular kinetochore functions to generate interactions between chromosomal DNA and spindle microtubules [1]. To facilitate chromosome movement and segregation, kinetochores must maintain associations with both growing and shrinking microtubule ends. It is critical to define the proteins and their properties that allow kinetochores to associate with dynamic microtubules. The kinetochore-localized human Ska1 complex binds to microtubules and tracks with depolymerizing microtubule ends [2]. We now demonstrate that the Ska1 complex also autonomously tracks with growing microtubule ends in vitro, a key property that would allow this complex to act at kinetochores to mediate persistent associations with dynamic microtubules. To define the basis for Ska1 complex interactions with dynamic microtubules, we investigated the tubulin-binding properties of the Ska1 microtubule binding domain. In addition to binding to the microtubule lattice and dolastatin-induced protofilament-like structures, we demonstrate that the Ska1 microtubule binding domain can associate with soluble tubulin heterodimers and promote assembly of oligomeric ring-like tubulin structures. We generated mutations on distinct surfaces of the Ska1 microtubule binding domain that disrupt binding to soluble tubulin, but do not prevent microtubule binding. These mutants display compromised microtubule tracking activity in vitro and result in defective chromosome alignment and mitotic progression in cells using a CRISPR/Cas9-based replacement assay. Our work supports a model in which multiple surfaces of Ska1 interact with diverse tubulin substrates to associate with dynamic microtubule polymers and facilitate optimal chromosome segregation.

show abstract

Section: Resultsmentioning

confidence: 99%

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Concomitantly, the Ska3 mutants deficient in Cdk1 phosphorylation failed to localize to kinetochores but retained their MT localization (Zhang et al, ). Contrary to these studies, fairly recently, an alternate mechanism for Ska recruitment to kinetochores was demonstrated via the N‐terminal unstructured tail of Ndc80 (Janczyk et al, ). Another study demonstrated that the direct interaction of the Ska complex (Ska1 subunit) with the MT plus‐end binding EB1 protein was responsible for the localization of Ska1 to the kMT interface (Thomas et al, ).…”

Section: Introductionmentioning

confidence: 95%

Mapping the kinetochore MAP functions required for stabilizing microtubule attachments to chromosomes during metaphase

2019

View full text Add to dashboard Cite

In mitosis, faithful chromosome segregation is orchestrated by the dynamic interactions between the spindle microtubules (MTs) emanating from the opposite poles and the kinetochores of the chromosomes. However, the precise mechanism that coordinates the coupling of the kinetochore components to dynamic MTs has been a long‐standing question. Microtubule‐associated proteins (MAPs) regulate MT nucleation and dynamics, MT‐mediated transport and MT cross‐linking in cells. During mitosis, MAPs play an essential role not only in determining spindle length, position, and orientation but also in facilitating robust kinetochore‐microtubule (kMT) attachments by linking the kinetochores to spindle MTs efficiently. The stability of MTs imparted by the MAPs is critical to ensure accurate chromosome segregation. This review primarily focuses on the specific function of nonmotor kinetochore MAPs, their recruitment to kinetochores and their MT‐binding properties. We also attempt to synthesize and strengthen our understanding of how these MAPs work in coordination with the kinetochore‐bound Ndc80 complex (the key component at the MT‐binding interface in metaphase and anaphase) to establish stable kMT attachments and control accurate chromosome segregation during mitosis.

show abstract

“…Therefore, it is still unclear how the Ska and Ndc80 complexes interact with one another at the atomic level and how these two complexes are organized in three dimensions. In spite of these findings, Ska kinetochore recruitment seems more complicated because of two recent studies suggesting that the Ndc80 N‐terminus also plays a role in recruiting Ska to kinetochores . Janczyk et al .…”

Section: How Is Ska Targeted To Kinetochores?mentioning

confidence: 99%

“…Janczyk et al . isolated an Ndc80 tail mutant that retained a robust microtubule‐binding capacity, but was deficient in clustering along microtubule protofilaments . As a result, this mutant recruited less Ska to the kinetochore.…”

Section: How Is Ska Targeted To Kinetochores?mentioning

confidence: 99%

Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions

2018

View full text Add to dashboard Cite

The human spindle and kinetochore associated (Ska) complex is required for proper mitotic progression. Extensive studies have demonstrated its important functions in both stable kinetochore-microtubule interactions and spindle checkpoint silencing. We suggest a model to explain how various Ska functions might be fulfilled by distinct pools of Ska at kinetochores. The Ndc80-loop pool of Ska is recruited by the Ndc80 loop, or together with some of its flanking sequences, and the recruitment is also dependent on Cdk1-mediated Ska3 phosphorylation. This pool seems to play a more important role in silencing the spindle checkpoint than stabilizing kinetochore-microtubule interactions. In contrast, the Ndc80-N-terminus pool of Ska is recruited by the N-terminal domains of Ndc80 and appears to be more important for stabilizing kinetochore-microtubule interactions. Here, we review and discuss the evidence that supports this model and suggest further experiments to test the functioning mechanisms of the Ska complex.

show abstract

Mechanism of Ska Recruitment by Ndc80 Complexes to Kinetochores

Cited by 51 publications

References 54 publications

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

Microtubule Tip Tracking by the Spindle and Kinetochore Protein Ska1 Requires Diverse Tubulin-Interacting Surfaces

Mapping the kinetochore MAP functions required for stabilizing microtubule attachments to chromosomes during metaphase

Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify Various Functions

Contact Info

Product

Resources

About