The kinetochore–microtubule interface at a glance

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Accurate chromosome segregation critically depends on the formation of attachments between microtubule polymers and each sister chromatid. The kinetochore is the macromolecular complex that assembles at the centromere of each chromosome during mitosis and serves as the link between the DNA and the microtubules. In this Cell Science at a Glance article and accompanying poster, we discuss the activities and molecular players that are involved in generating kinetochore–microtubule attachments, including the initial stages of lateral kinetochore–microtubule interactions and maturation to stabilized end-on attachments. We additionally explore the features that contribute to the ability of the kinetochore to track with dynamic microtubules. Finally, we examine the contributions of microtubule-associated proteins to the organization and stabilization of the mitotic spindle and the control of microtubule dynamics. Summary: Accurate chromosome segregation during cell division relies on attachments between the kinetochores and mitotic spindle microtubules. Here, we discuss the critical players at the kinetochore–microtubule interface.

Related collections

Most cited references 103

Record: found
Abstract: found
Article: not found

The conserved KMN network constitutes the core microtubule-binding site of the kinetochore.

Iain M. Cheeseman, Joshua S. Chappie, Elizabeth Wilson-Kubalek … (2006)

The microtubule-binding interface of the kinetochore is of central importance in chromosome segregation. Although kinetochore components that stabilize, translocate on, and affect the polymerization state of microtubules have been identified, none have proven essential for kinetochore-microtubule interactions. Here, we examined the conserved KNL-1/Mis12 complex/Ndc80 complex (KMN) network, which is essential for kinetochore-microtubule interactions in vivo. We identified two distinct microtubule-binding activities within the KMN network: one associated with the Ndc80/Nuf2 subunits of the Ndc80 complex, and a second in KNL-1. Formation of the complete KMN network, which additionally requires the Mis12 complex and the Spc24/Spc25 subunits of the Ndc80 complex, synergistically enhances microtubule-binding activity. Phosphorylation by Aurora B, which corrects improper kinetochore-microtubule connections in vivo, reduces the affinity of the Ndc80 complex for microtubules in vitro. Based on these findings, we propose that the conserved KMN network constitutes the core microtubule-binding site of the kinetochore.

0 comments Cited 345 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Kinetochore microtubule dynamics and attachment stability are regulated by Hec1.

Jennifer G. DeLuca, Walter E. Gall, Claudio Ciferri … (2006)

Mitotic cells face the challenging tasks of linking kinetochores to growing and shortening microtubules and actively regulating these dynamic attachments to produce accurate chromosome segregation. We report here that Ndc80/Hec1 functions in regulating kinetochore microtubule plus-end dynamics and attachment stability. Microinjection of an antibody to the N terminus of Hec1 suppresses both microtubule detachment and microtubule plus-end polymerization and depolymerization at kinetochores of PtK1 cells. Centromeres become hyperstretched, kinetochore fibers shorten from spindle poles, kinetochore microtubule attachment errors increase, and chromosomes severely mis-segregate. The N terminus of Hec1 is phosphorylated by Aurora B kinase in vitro, and cells expressing N-terminal nonphosphorylatable mutants of Hec1 exhibit an increase in merotelic attachments, hyperstretching of centromeres, and errors in chromosome segregation. These findings reveal a key role for the Hec1 N terminus in controlling dynamic behavior of kinetochore microtubules.

0 comments Cited 252 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

XMAP215 is a processive microtubule polymerase.

Gary J. Brouhard, Jeffrey Stear, Tim Noetzel … (2008)

Fast growth of microtubules is essential for rapid assembly of the microtubule cytoskeleton during cell proliferation and differentiation. XMAP215 belongs to a conserved family of proteins that promote microtubule growth. To determine how XMAP215 accelerates growth, we developed a single-molecule assay to visualize directly XMAP215-GFP interacting with dynamic microtubules. XMAP215 binds free tubulin in a 1:1 complex that interacts with the microtubule lattice and targets the ends by a diffusion-facilitated mechanism. XMAP215 persists at the plus end for many rounds of tubulin subunit addition in a form of "tip tracking." These results show that XMAP215 is a processive polymerase that directly catalyzes the addition of up to 25 tubulin dimers to the growing plus end. Under some circumstances XMAP215 can also catalyze the reverse reaction, namely microtubule shrinkage. The similarities between XMAP215 and formins, actin polymerases, suggest that processive tip tracking is a common mechanism for stimulating the growth of cytoskeletal polymers.