The MIS12 complex is a protein interaction hub for outer kinetochore assembly

Petrovic, Arsen; Pasqualato, Sebastiano; Dube, Prakash; Krenn, Veronica; Santaguida, Stefano; Cittaro, Davide; Monzani, Silvia; Massimiliano, Lucia; Keller, Jenny; Tarricone, Aldo; Maiolica, Alessio; Stark, Holger; Musacchio, Andrea

doi:10.1083/jcb.201002070

Cited by 211 publications

(304 citation statements)

References 85 publications

(181 reference statements)

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“…1B), our lysine-specific cross-linker provided limited information about MIND-Spc25 interactions. Previous work identified the C-terminal region of Dsn1 as being important for interaction with Spc24 and Spc25 and suggested that it also shares the binding site with Cnn1 (20,22). Our cross-linking results support this interaction although we detected far fewer cross-links between Dsn1 and Spc24 than between Nsl1 or Mtw1 and Spc24.…”

Section: Resultssupporting

confidence: 45%

“…S1). By pairing gel filtration and velocity sedimentation experiments, we found that MN exhibits a frictional ratio of 2.7 (19), consistent with its extremely elongated conformation as seen previously by negative-stain electron microscopy (17,18,20) (Fig. S1).…”

Section: Resultsmentioning

confidence: 49%

“…This identification of a second unique interface suggests that the Ndc80 complex may differentially interact with MIND and Cnn1, raising the possibility that each receptor might distinctly regulate Ndc80c function. Furthermore, Nsl1 has been identified as a link between human Mis12 and Ndc80 complexes (20), and our identification of its important contribution to the yeast MIND/Ndc80 interface establishes the structural conservation of this connection. Using single-molecule techniques, we show that the MIND complex promotes the binding of Ndc80c to microtubules.…”

Section: Mind Activates Microtubule Binding By Ndc80c Via a Mechanismmentioning

confidence: 94%

“…It is unknown whether MIND can similarly influence the behavior of the Ndc80 complex. In nematodes, the MIND and Ndc80 complexes do not directly interact without Knl1, but they do form a stable cocomplex in many other organisms, including yeast and humans (17,18,20). We therefore assessed how the MIND complex influences Ndc80 complex microtubule binding at the singlemolecule level using total internal reflection fluorescence (TIRF) microscopy.…”

Section: Mind Activates Microtubule Binding By Ndc80c Via a Mechanismmentioning

confidence: 99%

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Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

Kudalkar

Scarborough

Umbreit

et al. 2015

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

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Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore-microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubulebinding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex.

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Section: Resultssupporting

confidence: 45%

Section: Resultsmentioning

confidence: 49%

Section: Mind Activates Microtubule Binding By Ndc80c Via a Mechanismmentioning

confidence: 94%

Section: Mind Activates Microtubule Binding By Ndc80c Via a Mechanismmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

Kudalkar

Scarborough

Umbreit

et al. 2015

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

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“…This gradient of concentration is illustrated in orange. When the nuclear envelope breaks down, spindle subunits are preferentially assembled where the concentration of RanGTP is high (Spc25), which face the inner kinetochore and interact with minichromosome instability 12 (Mis12) complex (Petrovic et al 2010;Maskell et al 2010). Recent studies showed that an oligomeric array of Ndc80 complexes move along the microtubules through biased diffusion (Powers et al 2009;Alushin et al 2010).…”

Section: Kinetochores: a Re-evaluationmentioning

confidence: 99%

Mechanisms of plant spindle formation

Zhang

Dawe

2011

Chromosome Res

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In eukaryotes, the formation of a bipolar spindle is necessary for the equal segregation of chromosomes to daughter cells. Chromosomes, microtubules and kinetochores all contribute to spindle morphogenesis and have important roles during mitosis. A unique property of flowering plant cells is that they entirely lack centrosomes, which in animals have a major role in spindle formation. The absence of these important structures suggests that plants have evolved novel mechanisms to assure chromosome segregation. In this review, we highlight some of the recent studies on plant mitosis and argue that plants utilize a variation of "spindle self-organization" that takes advantage of the early polarity of plant cells and accentuates the role of kinetochores in stabilizing the spindle midzone in prometaphase.

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Adaptive Evolution of Centromeric Proteins

Roach

Ross

Malik

2011

Encyclopedia of Life Sciences

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Kinetochore proteins assemble at centromeres and mediate chromosome segregation during eukaryotic cell division. This conserved function conceals a paradox; essential inner kinetochore proteins, CenH3 and CENP‐C, evolve rapidly under positive selection in primates, plants and insects. This paradox may be explained by a genetic conflict between selfish DNA sequences at the centromere and the kinetochore proteins that bind them. The centromere drive hypothesis provides a framework for understanding this conflict and makes predictions for patterns of evolution in the composition of the kinetochore. In contrast with the rapidly evolving inner kinetochore, the components of the outer kinetochore do not make contacts with centromeric DNA and evolve more slowly. Furthermore, genetic conflict at the centromere may underlie observed taxonomic differences in the rate of evolution of kinetochore proteins among species with different meiotic programs. Key Concepts: Despite an essential and conserved function, some centromere‐binding proteins evolve rapidly. In contrast to canonical histone H3, the centromeric variant of histone H3 displays striking patterns of positive selection in functionally critical domains. CENP‐C displays rapid evolution across a diverse taxa; the functional consequences of this rapid evolution have not yet been studied. Asymmetric female meiosis provides an opportunity for competition among centromeres for evolutionary success but has deleterious consequences in male meiosis leading to genetic conflict. Genetic conflict between centromeres and centromere‐binding proteins can explain the divergent patterns of evolution between inner and outer kinetochore proteins, as well as taxonomic differences in rapid evolution of centromeric proteins.

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The MIS12 complex is a protein interaction hub for outer kinetochore assembly

Abstract: The NSL1 subunit structures interactions between the MIS12, NDC80, and KNL1 kinetochore complexes (see also a related paper by Maskell et al. in this issue).

Cited by 211 publications

References 85 publications

Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

Mechanisms of plant spindle formation

Adaptive Evolution of Centromeric Proteins

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