Full-length dimeric MCAK is a more efficient microtubule depolymerase than minimal domain monomeric MCAK.

MCAK belongs to the Kinesin-13 family, whose members depolymerize microtubules rather than translocate along them. We defined the minimal functional unit of MCAK as the catalytic domain plus the class specific neck (MD-MCAK), which is consistent with previous reports. We used steady-state ATPase kinetics, microtubule depolymerization assays, and microtubule.

Kinetochore-spindle microtubule interactions during mitosis.

The kinetochore is a proteinaceous structure that assembles onto centromeric DNA and mediates chromosome attachment to microtubules during mitosis. This description is deceivingly simple: recent proteomic studies suggest that the diminutive kinetochores of Saccharomyces cerevisiae are comprised of at least 60 proteins organized into as many as 14 different subcomplexes. Many of these proteins, such as the centromeric histone variant CENP-A, and entire subcomplexes, such as the Ndc80(Hec1) complex, are conserved from yeast to humans despite the diverse nature of the DNA sequences on which they assemble.

Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics.

The quest to find the underlying mechanisms of mitosis has taken many turns, which have largely been directed by the development of sensitive microscopes, enhanced microtubule-labeling techniques, advances in tubulin biochemistry, and genome-wide surveys to find the molecular "missing pieces" to the puzzle. Much of the work over the past decade has focused on the role of molecular motors in producing the necessary forces for spindle assembly and chromosome segregation. Recently, there has been a resurgence in research directed at understanding the intricate regulation of microtubule dynamics and organization during mitosis.

Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity.

Background: Sister kinetochores must bind microtubules in a bipolar fashion to equally segregate chromosomes during mitosis. The molecular mechanisms underlying this process remain unclear. Aurora B likely promotes chromosome biorientation by regulating kinetochore-microtubule attachments.

Depletion of centromeric MCAK leads to chromosome congression and segregation defects due to improper kinetochore attachments.

The complex behavior of chromosomes during mitosis is accomplished by precise binding and highly regulated polymerization dynamics of kinetochore microtubules. Previous studies have implicated Kin Is, unique kinesins that depolymerize microtubules, in regulating chromosome positioning. We have characterized the immunofluorescence localization of centromere-bound MCAK and found that MCAK localized to inner kinetochores during prophase but was predominantly centromeric by metaphase.

The microtubule-destabilizing kinesin XKCM1 is required for chromosome positioning during spindle assembly.

Xenopus kinesin catastrophe modulator-1 (XKCM1) is a Kin I kinesin family member that uses the energy of ATP hydrolysis to depolymerize microtubules. We demonstrated previously that XKCM1 is essential for mitotic-spindle assembly in vitro and acts by regulating microtubule dynamics as a pure protein, in extracts and in cells. A portion of the XKCM1 pool is specifically localized to centromeres during mitosis and may be important in chromosome movement.

The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells.

The dynamic activities of cellular microtubules (MTs) are tightly regulated by a balance between MT-stabilizing and -destabilizing proteins. Studies in Xenopus egg extracts have shown that the major MT destabilizer during interphase and mitosis is the kinesin-related protein XKCM1, which depolymerizes MT ends in an ATP-dependent manner. Herein, we examine the effects of both overexpression and inhibition of XKCM1 on the regulation of MT dynamics in vertebrate somatic cells.