Cytokinesis-Based Constraints on Polarized Cell Growth in Fission Yeast

Howard Hughes Medical Institute and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
PLoS Genetics (Impact Factor: 7.53). 10/2012; 8(10):e1003004. DOI: 10.1371/journal.pgen.1003004
Source: PubMed


The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in the ensuing cell cycle. Complete loss or targeted disruption of the non-essential cytokinesis protein Fic1 at the division site, but not at interphase cell tips, resulted in many cells failing to grow at new ends created by cell division. This appeared due to faulty disassembly and abnormal persistence of the cell division machinery at new ends of fic1Δ cells. Moreover, additional mutants defective in the final stages of cytokinesis exhibited analogous growth polarity defects, supporting that robust completion of cell division contributes to new end-growth competency. To test this model, we genetically manipulated S. pombe cells to undergo new end take-off immediately after cell division. Intriguingly, such cells elongated constitutively at new ends unless cytokinesis was perturbed. Thus, cell division imposes constraints that partially override positive controls on growth. We posit that such constraints facilitate invasive fungal growth, as cytokinesis mutants displaying bipolar growth defects formed numerous pseudohyphae. Collectively, these data highlight a role for previous cell cycles in defining a cell's capacity to polarize at specific sites, and they additionally provide insight into how a unicellular yeast can transition into a quasi-multicellular state.

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    • "The polarity defects in gef3∆ cdc42-1625 and gef3∆ for3∆ (Table 1 and Supplemental Figure S2A) suggest that Gef3 also has a function in cell polarity. Although Gef3 only localizes to the division site and transiently to the new cell ends, its role in cell polarization is consistent with growth-polarity defects reported in mutants with defects in final stages of cytokinesis (Bohnert and Gould, 2012). Alternatively , Gef3 and Rho4 may indirectly regulate cell polarity by affecting exocystdependent delivery of vesicles to polarized growth sites, especially given that gef3∆ and rho4∆ are both synthetic sick with myo52∆, a mutant defective in long-distance vesicle transport along actin cables (Win et al., 2001; Bendezú and Martin, 2011). "
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    ABSTRACT: Rho GTPases, activated by Rho guanine nucleotide exchange factors (GEFs), are conserved molecular switches for signal transductions that regulate diverse cellular processes including cell polarization and cytokinesis. The fission yeast Schizosaccharomyces pombe has six Rho GTPases (Cdc42 and Rho1-Rho5) and seven Rho GEFs (Scd1, Rgf1-Rgf3, and Gef1-Gef3). The GEFs for Rho2-Rho5 have not been unequivocally assigned. Particularly, Gef3, the smallest Rho GEF, was barely studied. Here we show that Gef3 colocalizes with septins at the cell equator. Gef3 physically interacts with septins and anillin Mid2 and depends on them to localize. Gef3 coprecipitates with GDP-bound Rho4 in vitro and accelerates nucleotide exchange of Rho4, suggesting that Gef3 is a GEF for Rho4. Consistently, Gef3 and Rho4 are in the same genetic pathways to regulate septum formation and/or cell separation. In gef3∆ cells, the localizations of two potential Rho4 effectors, glucanases Eng1 and Agn1, are abnormal; and active Rho4 level is reduced, indicating that Gef3 is involved in Rho4 activation in vivo. Moreover, overexpression of active Rho4 or Eng1 rescues the septation defects of mutants containing gef3∆. Together, our data support that Gef3 interacts with the septin complex and activates Rho4 GTPase as a Rho GEF for septation in fission yeast. © 2014 by The American Society for Cell Biology.
    Molecular Biology of the Cell 11/2014; 26(2). DOI:10.1091/mbc.E14-07-1196 · 4.47 Impact Factor
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    ABSTRACT: Polarization is a fundamental cellular property, which is essential for the function of numerous cell types. Over the past three to four decades, research using the best-established yeast systems in cell biological research, Saccharomyces cerevisiae (or budding yeast) and Schizosaccharomyces pombe (or fission yeast), have brought to light fundamental principles governing the establishment and maintenance of a polarized, asymmetric state. These two organisms, though both ascomycetes, are evolutionarily very distant and exhibit distinct shapes and modes of growth. In this review, we compare and contrast the two systems. We first highlight common cell polarization pathways, detailing the contribution of Rho GTPases, the cytoskeleton, membrane trafficking, lipids and protein scaffolds. We then contrast the major differences between the two organisms, describing their distinct strategies in growth site selection and growth zone dimensions and compartmentalization, which may be the basis for their distinct shapes. This article is protected by copyright. All rights reserved.
    FEMS microbiology reviews 12/2013; 38(2). DOI:10.1111/1574-6976.12055 · 13.24 Impact Factor
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    ABSTRACT: F-BAR domain proteins act as linkers between the cell cortex and cytoskeleton and are involved in membrane binding and bending. Rga7 is one of the seven F-BAR proteins present in fission yeast. In addition to the F-BAR domain at the N-terminal region, Rga7 possesses a Rho-GAP domain at its C-terminus. We show here that Rga7 is necessary to prevent contracting ring fragmentation and incorrect septum synthesis. Accordingly, cultures of cells lacking Rga7 contain a higher percentage of dividing cells and more frequent asymmetric or aberrant septa, which ultimately may cause cell death. Rga7 F-BAR domain is necessary for the protein localization to the division site and to the cell tips and also for the Rga7 roles in cytokinesis. In contrast, Rga7 GAP catalytic activity seems to be dispensable. Moreover, we demonstrate that Rga7 cooperates with the two F-BAR proteins Cdc15 and Imp2 to ensure proper cytokinesis. We have also detected association of Rga7 with Imp2, and its binding partners Fic1 and Pxl1. Altogether, our findings suggest that Rga7 forms part of a protein complex that coordinates late stages of cytokinesis.
    Journal of Cell Science 07/2014; 127(19). DOI:10.1242/jcs.146233 · 5.43 Impact Factor
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