SIN-Inhibitory Phosphatase Complex Promotes Cdc11p Dephosphorylation and Propagates SIN Asymmetry in Fission Yeast

Abstract

Background Cytokinesis in many eukaryotes involves the function of an actomyosin-based contractile ring. In fission yeast, actomyosin ring maturation and stability require a conserved signaling pathway termed the SIN (septation initiation network). The SIN consists of a GTPase (Spg1p) and three protein kinases, all of which localize to the mitotic spindle pole bodies (SPBs). Two of the SIN kinases, Cdc7p and Sid1p, localize asymmetrically to the newly duplicated SPB in late anaphase. How this asymmetry is achieved is not understood, although it is known that their symmetric localization impairs cytokinesis. Results Here we characterize a new Forkhead-domain-associated protein, Csc1p, and identify SIN-Inhibitory PP2A-complex (SIP), which is crucial for the establishment of SIN asymmetry. Csc1p localizes to both SPBs early in mitosis, is lost from the SPB that accumulates Cdc7p, and instead accumulates at the SPB lacking Cdc7p. Csc1p is required for the dephosphorylation of the SIN scaffolding protein Cdc11p and is thereby required for the recruitment of Byr4p, a component of the GTPase-activating subunit for Spg1p, to the SPB. Conclusions Since Cdc7p does not bind to GDP-Spg1p, we propose that the SIP-mediated Cdc11p-dephosphorylation and the resulting recruitment of Byr4p are amongst the earliest steps in the establishment of SIN asymmetry.

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

“…Five of six SIP components are even conserved from yeast to man [69]. On one hand, this suggests that the STRIPAK complex perhaps regulates Hippo in mitosis as observed for the regulation of the Hippo analogue Sid1p by SIP [69]. On the other hand, these reports emphasise that in animal cells it will not be sufficient to focus on Cdc14 when addressing the regulation of mitotic exit by phosphatases.…”

“…Intriguingly, in fission yeast the SIN is regulated by an SINinhibitory PP2A phosphatase (SIP) complex that is very similar to the STRIPAK complex [69]. Five of six SIP components are even conserved from yeast to man [69]. On one hand, this suggests that the STRIPAK complex perhaps regulates Hippo in mitosis as observed for the regulation of the Hippo analogue Sid1p by SIP [69].…”

“…Ribeiro et al (2010) reported that Hippo signalling is negatively regulated by the STRIPAK complex, which contains a functional PP2A unit [68]. Intriguingly, in fission yeast the SIN is regulated by an SINinhibitory PP2A phosphatase (SIP) complex that is very similar to the STRIPAK complex [69]. Five of six SIP components are even conserved from yeast to man [69].…”

Tiered Assembly of the Yeast Far3-7-8-9-10-11 Complex at the Endoplasmic Reticulum

“…Apart from the ER localization of human and S. cerevisiae STRIPAK components, two components of the fission yeast S. pombe STRIPAK complex, Csc2 and Csc3 (S. cerevisiae Far11 and Far8 orthologs, respectively), also associate with the nuclear envelope/ER. Conversely, Csc1, the S. cerevisiae Far9/10 ortholog, was not found to localize to the nuclear envelope (20). However, this could be due to the addition of GFP at its C terminus, which interferes with its tail-anchor domain-dependent ER localization.…”

“…In the ascomycete Sordaria macrospora, the STRIPAK complex is required for sexual development and vegetative hyphal fusion (18,19). In the fission yeast Schizosaccharomyces pombe, components of the STRIPAK complex localize to the mitotic spindle pole body in early mitosis and are required for the establishment of asymmetry of the septation initiation network, a conserved signaling pathway that is required for cytokinesis and mitotic transitions (9,20).…”