Indeed, our follow-up study showed that SKAP interacts with MIS13 and this interaction specifies the kinetochore localization of SKAP ( Wang et al., 2012), which functions as a linker protein connecting the outer kinetochore with dynamic microtubule plus-ends. Interestingly, suppression of CENP-E does not abolish the kinetochore localization of SKAP, raising interest in the identification of the kinetochore constituent(s) that specifies SKAP localization to the kinetochore. Our early study showed that SKAP cooperates with CENP-E to orchestrate kinetochore–microtubule interaction for faithful chromosome segregation ( Huang et al., 2012). SKAP forms functional complexes with Astrin and the mitotic kinesin CENP-E, respectively ( Thein et al., 2007 Huang et al., 2012). An efficient coupling requires three or more NDC80 complexes bound to CENP-T, suggesting the importance of multivalency in end-on capture of kinetochore microtubules.Īn early search for conversion of lateral to end-on capture regulators has led to the identification of SKAP as an outer kinetochore protein that is essential for chromosome alignment ( Fang et al., 2009 Wang et al., 2012). However, using recombinant human kinetochore components, it was shown that single NDC80 complexes do not track depolymerizing microtubules ( Volkov et al., 2018). Mounting evidence supports the critical role of KNL1‒Mis12‒Ndc80 complex in coupling spindle microtubule plus-ends to the kinetochore ( Cheeseman and Desai, 2008 DeLuca, 2010 Foley and Kapoor, 2013 Hara and Fukagawa, 2017). The kinetochore acts as a structural platform for linking the centromere to spindle microtubules and functions as a signaling hub coordinating chromosome attachment and the metaphase-to-anaphase transition ( Bakhoum et al., 2009a, b Cheeseman, 2014 McKinley and Cheeseman, 2016). Accurate chromosome attachment to lateral spindle microtubules and subsequent conversion to end-on capture are essential for genomic stability in mitosis ( Shrestha et al., 2017 Huang et al., 2019). Based on those findings, we reason that SKAP–Aurora B interaction via phase separation constitutes a dynamic pool of Aurora B activity during the lateral to end-on conversion of kinetochore–microtubule attachments to achieve faithful cell division.Īurora B, SKAP, kinase activity, mitosis, phase separation IntroductionĮrror-free mitosis depends on accurate chromosome attachment to spindle microtubules, end-on capture of kinetochore microtubules, and powered congression of those chromosomes prior to chromatid segregation in anaphase ( Cleveland et al., 2003 Foley and Kapoor, 2013 McKinley and Cheeseman, 2016 Liu et al., 2020). Importantly, SKAP interaction with Aurora B via phase separation is essential for accurate chromosome segregation and alignment. SKAP and Aurora B form heterogeneous coacervates in vitro, which recapitulate the dynamics and behavior of SKAP comets in vivo. Interestingly, SKAP spontaneously phase-separates in vitro via weak, multivalent interactions into droplets with fast internal dynamics. Here, we identify a novel interaction between Aurora B and SKAP that orchestrates accurate interaction between the kinetochore and dynamic spindle microtubules. However, it remains elusive how SKAP regulates kinetochore attachment from lateral association to end-on attachment during metaphase alignment. Our recent studies show that mitotic motor CENP-E cooperates with SKAP and forms a link between kinetochore core MIS13 complex and spindle microtubule plus-ends to achieve accurate chromosome alignment in mitosis. Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules.
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