B56-PP2A regulates motor dynamics for mitotic chromosome alignment

Abstract

Proper alignment of duplicated chromosomes at the metaphase plate involves both motor-driven chromosome movement and the functional and physical end-on connection (K-fiber formation) between the kinetochore and the plus-end of microtubules. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits (B56-PP2A), through their interaction with the mitotic checkpoint protein BUBR1, are required for proper chromosome alignment, but the underlying mechanism(s) has remained elusive. Here, we show that B56-PP2A promotes chromosome alignment primarily by balancing chromosome movement towards the metaphase plate, rather than by directly establishing stable K-fibers. Notably, the poleward movement of chromosomes in cells depleted of the B56 family can be rescued by depletion of HSET (also known as kinesin-14 or KIFC1), a major minus-end-directed motor protein. Strikingly, K-fiber formation can be restored if chromosome movement to the metaphase plate is rescued in B56-depleted cells. Furthermore, the B56-BUBR1 interaction is required for promoting motor-driven chromosome movement towards the metaphase plate. Thus, we propose that B56-PP2A functions in mitotic chromosome alignment by balancing chromosome movement towards the metaphase plate, which is essential for the subsequent establishment of stable and functional kinetochore-microtubule attachments, and mitotic exit.

Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest

“…In mitotic cells, BubR1-associated PP2A-B56 was shown to promote chromosome movements to the metaphase plate and the formation of stable kinetochore fibres by counteracting HSET/kinesin-14, a minus end directed motor protein 52 . It remains to be addressed whether in meiosis BubR1-associated PP2A targets this and other motor proteins, in a kinetochore-independent manner.…”

PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte

“…A recent study in mitosis suggests that PP2A regulate HSET to balance chromosome movement toward the metaphase plate. 39 It is worth determining whether HSET play a similar role in oocyte meiosis I.…”

Two spatially distinct Kinesin-14 Pkl1 and Klp2 generate collaborative inward forces against Kinesin-5 Cut7 inS. pombe

“…However, there are several features that are shared by Klp2 and HSET, but not by Pkl1, including microtubule-bundling activity (Braun et al, 2009; Cai et al, 2009; Carazo-Salas et al, 2005; Carazo-Salas and Nurse, 2006; Daga et al, 2006), a direct interaction with the microtubule plus end tracking proteins EB1/Mal3 (Braun et al, 2013; Mana-Capelli et al, 2012; Scheffler et al, 2015) and kinetochore localization (Xu et al, 2014). We ponder the idea that fission yeast has evolved to be equipped with two spatially distinct Kinesin-14s, both of which retain some functional features of human HSET.…”