Chromokinesins: Localization-dependent functions and regulation during cell division

Centre for Genomic Regulation and Universitat Pompeu Fabra, Barcelona, Spain.
Biochemical Society Transactions (Impact Factor: 3.19). 10/2011; 39(5):1154-60. DOI: 10.1042/BST0391154
Source: PubMed


The bipolar spindle is a highly dynamic structure that assembles transiently around the chromosomes and provides the mechanical support and the forces required for chromosome segregation. Spindle assembly and chromosome movements rely on the regulation of microtubule dynamics and a fine balance of forces exerted by various molecular motors. Chromosomes are themselves central players in spindle assembly. They generate a RanGTP gradient that triggers microtubule nucleation and stabilization locally and they interact dynamically with the microtubules through motors targeted to the chromatin. We have previously identified and characterized two of these so-called chromokinesins: Xkid (kinesin 10) and Xklp1 (kinesin 4). More recently, we found that Hklp2/kif15 (kinesin 12) is targeted to the chromosomes through an interaction with Ki-67 in human cells and is therefore a novel chromokinesin. Hklp2 also associates with the microtubules specifically during mitosis, in a TPX2 (targeting protein for Xklp2)-dependent manner. We have shown that Hklp2 participates in spindle pole separation and in the maintenance of spindle bipolarity in metaphase. To better understand the function of Hklp2, we have performed a detailed domain analysis. Interestingly, from its positioning on the chromosome arms, Hklp2 seems to restrict spindle pole separation. In the present review, we summarize the current knowledge of the function and regulation of the different kinesins associated with chromosome arms during cell division, including Hklp2 as a novel member of this so-called chromokinesin family.

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    • "Chromokinesins associate with both chromosomal DNA and spindle microtubules during mitosis and are implicated in various functions during mitosis (Fig. 1F). In metazoans, there are three families of chromokinesins (Kinesin-4, -10, and -12) that are important for bipolar spindle formation, chromosome condensation, chromosome alignment, and chromosome segregation [Mazumdar and Misteli, 2005; Vanneste et al., 2011]. The Kinesin-12 family chromokinesin Kif15 is important for maintaining bipolar spindle assembly, particularly in absence of Eg5 [Tanenbaum et al., 2009; Vanneste et al., 2009]. "
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    ABSTRACT: Microtubule-based motor proteins play key roles during mitosis to assemble the bipolar spindle, define the cell division axis, and align and segregate the chromosomes. The majority of mitotic motors are members of the kinesin superfamily. Despite sharing a conserved catalytic core, each kinesin has distinct functions and localization, and is uniquely regulated in time and space. These distinct behaviors and functional specificity are generated by variations in the enzymatic domain as well as the non-conserved regions outside of the kinesin motor domain and the stalk. These flanking regions can directly modulate the properties of the kinesin motor through dimerization or self-interactions, and can associate with extrinsic factors, such as microtubule or DNA binding proteins, to provide additional functional properties. This review discusses the recently identified molecular mechanisms that explain how the control and functional specification of mitotic kinesins is achieved. © 2013 Wiley Periodicals, Inc.
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    ABSTRACT: The mitotic spindle is structurally and functionally defined by its main component, the microtubules (MTs). The MTs making up the spindle have various functions, organization and dynamics: astral MTs emanate from the centrosome and reach the cell cortex, and thus have a major role in spindle positioning; interpolar MTs are the main constituent of the spindle and are key for the establishment of spindle bipolarity, chromosome congression and central spindle assembly; and kinetochore-fibers are MT bundles that connect the kinetochores with the spindle poles and segregate the sister chromatids during anaphase. The duplicated centrosomes were long thought to be the origin of all of these MTs. However, in the last decade, a number of studies have contributed to the identification of non-centrosomal pathways that drive MT assembly in dividing cells. These pathways are now known to be essential for successful spindle assembly and to participate in various processes such as K-fiber formation and central spindle assembly. In this Commentary, we review the recent advances in the field and discuss how different MT assembly pathways might cooperate to successfully form the mitotic spindle.
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