The phosphatase inhibitor Sds23 regulates cell division symmetry in fission yeast

Abstract

Animal and fungal cells divide through the assembly, anchoring, and constriction of a contractile actomyosin ring (CAR) during cytokinesis. The timing and position of the CAR must be tightly controlled to prevent defects in cell division, but many of the underlying signaling events remain unknown. The conserved heterotrimeric protein phosphatase PP2A controls the timing of events in mitosis, and upstream pathways including Greatwall–Ensa regulate PP2A activity. A role for PP2A in CAR regulation has been less clear, although loss of PP2A in yeast causes defects in cytokinesis. Here, we report that Sds23, an inhibitor of PP2A family protein phosphatases, promotes the symmetric division of fission yeast cells through spatial control of cytokinesis. We found that sds23∆ cells divide asymmetrically due to misplaced CAR assembly, followed by sliding of the CAR away from its assembly site. These mutant cells exhibit delayed recruitment of putative CAR anchoring proteins including the glucan synthase Bgs1. Our observations likely reflect a broader role for regulation of PP2A in cell polarity and cytokinesis because sds23∆ phenotypes were exacerbated when combined with mutations in the fission yeast Ensa homologue, Igo1. These results identify the PP2A regulatory network as a critical component in the signaling pathways coordinating cytokinesis.

The phosphatase inhibitor Sds23 promotes symmetric spindle positioning in fission yeast

“…In this study, we have identified a role for Sds23, a PP2A-family phosphatase inhibitor, in symmetric elongation of mitotic spindles in fission yeast. Past studies have shown a role for Sds23 in cell polarity and nutrient sensing (Deng, Lee, Schutt, & Moseley, 2017;Hanyu et al, 2009;Ishii, Kumada, Toda, & Yanagida, 1996), and we recently showed that Sds23 promotes positioning and anchoring of the cytokinetic ring in the cell middle (Schutt & Moseley, 2019). Here, we find that anaphase spindles elongate asymmetrically in sds23Δ cells, often fully entering one-half of the dividing cell.…”

“…Sds23 inhibits both Protein Phosphatase 6 (PP6) and Protein Phosphatase 2A (PP2A) (Deng et al, 2017;Hanyu et al, 2009;Schutt & Moseley, 2019). In fission yeast, both PP6 and PP2A-B55 (Pab1) are enriched in the nucleus, and PP2A-B56 (Par1) localizes to the SPBs during mitosis (Deng et al, 2017;Goshima, Iwasaki, Obuse, & Yanagida, 2003;Lahoz, Alcaide-Gavilán, Daga, & Jimenez, 2010;Le Goff et al, 2001).…”