Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes

Abstract

Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2’s ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation.Human reproductive cells—eggs and sperm—are produced through a process called meiosis. This means a ‘parent’ cell in the ovaries or testes undergoes two stages of cell division: it first divides into two cells, which then divide again to produce four ‘daughter’ cells. A crucial part of meiosis is ensuring that each daughter cell has half the number of chromosomes that the parent cell did.Before the first round of meiosis, the chromosomes in the parent cell are copied to produce enough chromosomes for the four daughter cells. The distribution of these chromosomes between the daughter cells is determined by the opposing forces acting on them. The pairs of identical chromosomes produced during the copying process are held together by a proteinaceous glue, while microtubules attached to a structure called the spindle—which has poles at opposite ends of the cell—try to pull these pairs of chromosomes apart.Rattani et al. now show that a protein called shugoshin-like 2 (Sgol2), which is involved in holding pairs of identical chromosomes together after the first round of division, has a bigger role than was previously realised. Sgol2 performs three other functions: it helps to align the chromosomes prior to division by, it is thought, facilitating the formation of the K-fibers that attach the microtubules to the chromosomes; it turns off the checkpoint that monitors the alignment of the chromosomes and the attachment of the microtubules; and it regulates a number of the enzymes involved in the process. The specific interactions that allow Sgol2 to perform these diverse functions in meiosis were also identified. Thus, Rattani et al. show that in linking so many essential processes throughout meiosis, Sgol2 appears to have a key, if not unique, role in determining the fate of chromosomes as cells divide.