A Perikinetochoric Ring Defined by MCAK as a New Centromere Domain in Meiosis

Abstract

Mitotic Centromere-Associated Kinesin (MCAK) is a member of the kinesin-13 subfamily of kinesin-related proteins. In mitosis, this microtubule-depolymerising kinesin seems to be implicated in chromosome segregation and in the correction of improper kinetochore-microtubule interactions, and its activity is regulated by the Aurora-B kinase. However, there are no published data on its behaviour and function during mammalian meiosis. We have analysed by immunofluorescence in squashed mouse spermatocytes, the distribution and possible function of MCAK, together with Aurora-B, during both meiotic divisions. Our results demonstrate that MCAK and Aurora-B colocalise at the inner domain of metaphase I centromeres. Thus, MCAK shows a ''cone''-like three-dimensional distribution beneath and surrounding the closely associated sister kinetochores. During the second meiotic division, MCAK and Aurora-B also colocalise at the inner centromere domain as a band that joins sister kinetochores, but only during prometaphase II in unattached chromosomes. During chromosome congression to the metaphase II plate, MCAK relocalises and appears as a ring below each sister kinetochore. Aurora-B also relocalises to appear as a ring surrounding and beneath kinetochores but during late metaphase II. Our results demonstrate that the redistribution of MCAK at prometaphase II/metaphase II centromeres depends on tension across the centromere and/or on the interaction of microtubules with kinetochores. We propose that the perikinetochoric rings of MCAK and Aurora-B define a novel transient centromere domain at least in mouse chromosomes during meiosis. We discuss the possible functions of MCAK at the inner centromere domain and at the perikinetochoric ring during both meiotic divisions.

Mammalian SGO2 appears at the inner centromere domain and redistributes depending on tension across centromeres during meiosis II and mitosis

“…Our data indicate that SGO2 redistributes from a band at the inner centromere domain to a ring below each sister kinetochore during chromosome congression to the metaphase II plate (supplementary Fig 5 online) and also during mitosis. We have recently reported a similar redistribution for the microtubule‐depolymerizing kinesin MCAK and the kinase Aurora B during meiosis II in the mouse (Parra et al , 2006). Moreover, SGO1 also redistributes at the centromeres during chromosome congression in HeLa cells (McGuinness et al , 2005).…”

“…Recently, it has been proposed that the microtubule‐depolymerizing kinesin mitotic centromere‐associated kinesin (MCAK), located at the inner centromere domain of mitotic chromosomes, is involved in the correction of improper kinetochore–microtubule interactions. MCAK redistributes at HeLa mitotic and mouse prometaphase II centromeres depending on tension across centromeres (Andrews et al , 2004; Parra et al , 2006); therefore, we double immunolabelled SGO2 and MCAK to test whether their redistribution was comparable. Our results showed that both proteins redistributed in a similar manner during chromosome congression at prometaphase II (Fig 4J–L′).…”

Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres

“…Because the PP2A localization at centromeres depends largely on mSgo2 protein in germ cells (Lee et al 2008), these results imply that the phosphorylation of mSgo2 by Aurora B is crucial for the localization of PP2A at centromeres. Given that MCAK also localizes at centromeres in germ cells (Parra et al 2006), we performed a comparable experiment using an MCAK antibody. The results similarly suggest that mSgo2 phosphorylation by Aurora B is important for the centromeric localization of MCAK (Fig.…”