scholarly journals Rho GTPases: regulation of cell polarity and growth in yeasts

2010 ◽  
Vol 426 (3) ◽  
pp. 243-253 ◽  
Author(s):  
Pilar Perez ◽  
Sergio A. Rincón
Keyword(s):  
Cell Wall ◽  
Cell Polarity ◽  
Rho Gtpases ◽  
Molecular Mechanisms ◽  
Eukaryotic Cells ◽  
Signalling Pathways ◽  
Polarized Growth ◽  
Cell Integrity ◽  
Actin Organization ◽  
Wide Range

Eukaryotic cells display a wide range of morphologies important for cellular function and development. A particular cell shape is made via the generation of asymmetry in the organization of cytoskeletal elements, usually leading to actin localization at sites of growth. The Rho family of GTPases is present in all eukaryotic cells, from yeast to mammals, and their role as key regulators in the signalling pathways that control actin organization and morphogenetic processes is well known. In the present review we will discuss the role of Rho GTPases as regulators of yeasts' polarized growth, their mechanism of activation and signalling pathways in Saccharomyces cerevisiae and Schizosaccharomyces pombe. These two model yeasts have been very useful in the study of the molecular mechanisms responsible for cell polarity. As in other organisms with cell walls, yeast's polarized growth is closely related to cell-wall biosynthesis, and Rho GTPases are critical modulators of this process. They provide the co-ordinated regulation of cell-wall biosynthetic enzymes and actin organization required to maintain cell integrity during vegetative growth.

scholarly journals Rho4 GTPase Is Involved in Secretion of Glucanases during Fission Yeast Cytokinesis

2005 ◽  
Vol 4 (10) ◽  
pp. 1639-1645 ◽  
Author(s):  
Beatriz Santos ◽  
Ana Belén Martín-Cuadrado ◽  
Carlos R. Vázquez de Aldana ◽  
Francisco del Rey ◽  
Pilar Pérez
Keyword(s):  
Cell Wall ◽  
Cell Polarity ◽  
Rho Gtpases ◽  
Culture Medium ◽  
Fluorescent Protein ◽  
Eukaryotic Cells ◽  
Glucanase Activity ◽  
Actin Organization ◽  
Cell Extracts ◽  
Green Fluorescent

ABSTRACT Rho GTPases are regulators of signaling pathways that control actin organization and cell polarity processes in all eukaryotic cells. In Schizosaccharomyces pombe, Rho4p is involved in the regulation of septum degradation during cytokinesis. Here we show that Rho4p participates in the secretion of the glucanases Eng1p and Agn1p, which are responsible for the septum degradation. First, eng1 + or agn1 + overexpression suppressed the rho4Δ multiseptation phenotype, and simultaneous overproduction of Rho4p and Eng1p or of Rho4p and Agn1p caused a dramatic lysis. Second, Rho4p was not necessary for Eng1p-mediated glucanase activity as measured in cell extracts; however, rho4Δ cells have a lower level of (1,3)-β-d-glucanase activity in the culture medium. Additionally, Eng1- or Agn1-green fluorescent protein did not properly localize to the septum in rho4Δ cells grown at 37°C. There was a decreased amount of these enzymes in the cell wall and in the culture medium of rho4Δ cells at 37°C. These results provide evidence that Rho4p is involved in the regulation of Eng1p and Agn1p secretion during cytokinesis.

scholarly journals Cell-Biological Studies of Osmotic Shock Response in Streptomyces spp

2016 ◽  
Vol 199 (1) ◽  
Author(s):  
Katsuya Fuchino ◽  
Klas Flärdh ◽  
Paul Dyson ◽  
Nora Ausmees
Keyword(s):  
Cell Wall ◽  
Cell Polarity ◽  
Tip Growth ◽  
Biological Study ◽  
Polar Growth ◽  
Hyphal Branching ◽  
Content Type ◽  
Biological Studies ◽  
Wide Range ◽  
Tip Extension

ABSTRACT Most bacteria are likely to face osmotic challenges, but there is yet much to learn about how such environmental changes affect the architecture of bacterial cells. Here, we report a cell-biological study in model organisms of the genus Streptomyces, which are actinobacteria that grow in a highly polarized fashion to form branching hyphae. The characteristic apical growth of Streptomyces hyphae is orchestrated by protein assemblies, called polarisomes, which contain coiled-coil proteins DivIVA and Scy, and recruit cell wall synthesis complexes and the stress-bearing cytoskeleton of FilP to the tip regions of the hyphae. We monitored cell growth and cell-architectural changes by time-lapse microscopy in osmotic upshift experiments. Hyperosmotic shock caused arrest of growth, loss of turgor, and hypercondensation of chromosomes. The recovery period was protracted, presumably due to the dehydrated state of the cytoplasm, before hyphae could restore their turgor and start to grow again. In most hyphae, this regrowth did not take place at the original hyphal tips. Instead, cell polarity was reprogrammed, and polarisomes were redistributed to new sites, leading to the emergence of multiple lateral branches from which growth occurred. Factors known to regulate the branching pattern of Streptomyces hyphae, such as the serine/threonine kinase AfsK and Scy, were not involved in reprogramming of cell polarity, indicating that different mechanisms may act under different environmental conditions to control hyphal branching. Our observations of hyphal morphology during the stress response indicate that turgor and sufficient hydration of cytoplasm are required for Streptomyces tip growth. IMPORTANCE Polar growth is an intricate manner of growth for accomplishing a complicated morphology, employed by a wide range of organisms across the kingdoms of life. The tip extension of Streptomyces hyphae is one of the most pronounced examples of polar growth among bacteria. The expansion of the cell wall by tip extension is thought to be facilitated by the turgor pressure, but it was unknown how external osmotic change influences Streptomyces tip growth. We report here that severe hyperosmotic stress causes cessation of growth, followed by reprogramming of cell polarity and rearrangement of growth zones to promote lateral hyphal branching. This phenomenon may represent a strategy of hyphal organisms to avoid osmotic stress encountered by the growing hyphal tip.

Rho family GTPases

2012 ◽  
Vol 40 (6) ◽  
pp. 1378-1382 ◽  
Author(s):  
Alan Hall
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Cellular Response ◽  
Molecular Switches ◽  
Effector Proteins ◽  
Eukaryotic Cells ◽  
Cell Behaviour ◽  
Wide Range ◽  
Rho Family Gtpases ◽  
Rho Family

Rho GTPases comprise a family of molecular switches that control signal transduction pathways in eukaryotic cells. A conformational change induced upon binding GTP promotes an interaction with target (effector) proteins to generate a cellular response. A highly conserved function of Rho GTPases from yeast to humans is to control the actin cytoskeleton, although, in addition, they promote a wide range of other cellular activities. Changes in the actin cytoskeleton drive many dynamic aspects of cell behaviour, including morphogenesis, migration, phagocytosis and cytokinesis, and the dysregulation of Rho GTPases is associated with numerous human diseases and disorders.

scholarly journals Evidence for a link between IGF-I and cancer

2004 ◽  
pp. S17-S22 ◽  
Author(s):  
PJ Jenkins ◽  
SA Bustin
Keyword(s):  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Normal Function ◽  
The Body ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Related Factors ◽  
Wide Range ◽  
Igf I ◽  
Inappropriate Expression

Cancer risk is determined by a combination of environmental factors and genetic predisposition. Recent evidence suggests that dietary and related factors such as physical activity and body size may influence cancer risk through their effects on the serum concentration of IGF-I and its binding proteins. The growth hormone (GH)/IGF-I axis is involved in both human development as well as the maintenance of normal function and homeostasis in most cells of the body. In addition to their classical role as endocrine hormones, its members regulate a wide range of biological functions such as cell proliferation, differentiation and apoptosis through paracrine and autocrine mechanisms. During cancer development this complex network regulating tissue homeostasis breaks down, with inappropriate expression of the GH/IGF-I axis making an important contribution. The increased understanding of the molecular mechanisms and signalling pathways regulated by the GH/IGF-I axis has started to provide significant insights into the aetiology, prevention and therapy for a number of common cancers.

scholarly journals The Role of the Cell Integrity Pathway in Septum Assembly in Yeast

2021 ◽  
Vol 7 (9) ◽  
pp. 729
Author(s):  
Cesar Roncero ◽  
Rubén Celador ◽  
Noelia Sánchez ◽  
Patricia García ◽  
Yolanda Sánchez
Keyword(s):  
Cell Wall ◽  
Map Kinases ◽  
Signalling Pathways ◽  
Cell Integrity ◽  
Animal Cells ◽  
Yeast Saccharomyces Cerevisiae ◽  
Downstream Effectors ◽  
Cell Wall Integrity Pathway ◽  
Extracellular Matrix Remodelling ◽  
Relationship Of

Cytokinesis divides a mother cell into two daughter cells at the end of each cell cycle and proceeds via the assembly and constriction of a contractile actomyosin ring (CAR). Ring constriction promotes division furrow ingression, after sister chromatids are segregated to opposing sides of the cleavage plane. Cytokinesis contributes to genome integrity because the cells that fail to complete cytokinesis often reduplicate their chromosomes. While in animal cells, the last steps of cytokinesis involve extracellular matrix remodelling and mid-body abscission, in yeast, CAR constriction is coupled to the synthesis of a polysaccharide septum. To preserve cell integrity during cytokinesis, fungal cells remodel their cell wall through signalling pathways that connect receptors to downstream effectors, initiating a cascade of biological signals. One of the best-studied signalling pathways is the cell wall integrity pathway (CWI) of the budding yeast Saccharomyces cerevisiae and its counterpart in the fission yeast Schizosaccharomyces pombe, the cell integrity pathway (CIP). Both are signal transduction pathways relying upon a cascade of MAP kinases. However, despite strong similarities in the assembly of the septa in both yeasts, there are significant mechanistic differences, including the relationship of this process with the cell integrity signalling pathways.

scholarly journals Mutations in a single signaling pathway allow growth on a different solvent than water

2019 ◽  
Author(s):  
Caroline Kampmeyer ◽  
Jens V. Johansen ◽  
Christian Holmberg ◽  
Magnus Karlson ◽  
Sarah K. Gersing ◽  
...  
Keyword(s):  
Cell Wall ◽  
Morphological Changes ◽  
Biological Effects ◽  
Control Cell ◽  
Wall Material ◽  
Cell Integrity ◽  
Prolonged Incubation ◽  
Altered Glucose ◽  
Wide Range ◽  
The Impact

AbstractSince life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O), and investigated the biological effects by a wide range of techniques, using the fission yeast Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that D2O causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several D2O sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genes pmk1, mkh1, pek1 and pck2, that control cell wall biogenesis, were more tolerant to D2O. We speculate that D2O affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the D2O-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects.

scholarly journals Dynamic, Rho1p-dependent localization of Pkc1p to sites of polarized growth

2000 ◽  
Vol 113 (15) ◽  
pp. 2685-2693 ◽  
Author(s):  
P.D. Andrews ◽  
M.J. Stark
Keyword(s):  
Cell Cycle ◽  
Cell Wall ◽  
Membrane Trafficking ◽  
Rho Gtpases ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Wall Stress ◽  
Live Cells ◽  
Polarized Growth ◽  
Temporal Localization

In eukaryotes, the Rho GTPases and their effectors are key regulators of the actin cytoskeleton, membrane trafficking and secretion, cell growth, cell cycle progression and cytokinesis. Budding yeast Pkc1p, a protein kinase C-like enzyme involved in cell wall biosynthesis and cytoskeletal polarity, is structurally and functionally related to the Rho-associated kinases (PRK/ROCK) of mammalian cells. In this study, localization of Pkc1p was monitored in live cells using a GFP fusion (Pkc1p-GFP). Pkc1p-GFP showed dynamic spatial and temporal localization at sites of polarized growth. Early in the cell cycle, Pkc1p-GFP was found at the pre-bud site and bud tips, becoming delocalized as the cell progressed further and finally relocalizing around the mother-daughter bud neck in an incomplete ring, which persisted until cell separation. Bud localization was actin-dependent but stability of Pkc1p-GFP at the neck was actin-independent, although localization at both sites required functional Rho1p. In addition, Pkc1p-GFP showed rapid relocalization after cell wall damage. These results suggest that the roles of Pkc1p in both polarized growth and the response to cell wall stress are mediated by dynamic changes in its localization, and suggest an additional potential role in cytokinesis.

Expression of the Cell Polarity Protein PTK7 in Acute Myeloid Leukaemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1478-1478
Author(s):  
Thomas Prebet ◽  
Anne Catherine Lhoumeau ◽  
Christine Arnoulet ◽  
Sylvie Marchetto ◽  
Christian Chabannon ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Leukemia Cell ◽  
Tyrosine Kinase Receptor ◽  
Low Grade ◽  
Potential Implication ◽  
Wide Range ◽  
Low Levels

Abstract The planar cell polarity pathway plays a major role in embryogenesis and tissue organisation. Recent genetic studies have highlighted the role of novel receptors and signaling molecules implicated in this pathway. Amongst the receptors, the pseudo tyrosine kinase receptor 7 (PTK7) is an orphean tyrosine kinase receptor with kinase-dead activity. Knock-out of PTK7 in mice strongly affects embryonic development leading to a major neural tube defect. Presence of PTK7 was previously investigated in epithelial and endothelial cells that both express the receptor. In normal donors, we found no expression of PTK7 in peripheral blood (n=5) whereas PTK7 expression was found with low levels in PBPC after G-CSF stimulation (n=3) and high levels in normal myeloid progenitors and CD34+ CD38− bone marrow cells (n=3). Overexpression of PTK7 was already described in solid tumors including breast, lung and pancreatic cancers. We decided to study the potential implication of PTK7 in haematological malignancies. We performed a wide range multicolour immunophenotyping screen on more than 240 patient samples treated at Institut Paoli-Calmettes and 10 leukemia cell lines. In hematologic malignancies, we demonstrated that PTK7 was widely expressed in AML (136 of 195 patients) and in the most immature subsets of Acute lymphoblastic (5 of 20 patients) or biphenotypic leukaemia (3 of 3 patients). We found no expression of PTK7 in chronic disorder such low grade NHL (n=7), CLL (n=6) or Chronic Myelomonocytic Leukemia (n=3). In AML, we demonstrated that PTK7 expression mostly correlates with granulocytic lineage differentiation and that it could be partially expressed in AML 4 or 5 subsets. Flow cytometry analysis confirmed the co-expression of PTK7 with granulocytic lineage markers and that PTK7 expression in myelomonocytic leukaemia was limited to the myeloid subset of blasts. The strongest immunophenotyping correlation was found with CD117/c-Kit expression (p<0.001) and PTK7 Mean Fluorescence Intensity directly correlates with c-Kit MFI (p=0.001). Interestingly, stimulation of cultured TF1 cells (that endogenously express c-Kit and PTK7) with SCF triggered an increased expression of PTK7. Correlation between PTK7 expression and biological or clinical features was also evaluated. We demonstrated that PTK7 expression clustered with some cytogenetic subsets (high levels in CBF AML (n=19) or APL (n=13), low levels in FLT3 mutated AML(n=17) or complex karyotype (n=20)). We also found that PTK7 expression was associated with a lower WBC count at diagnosis (p=0.001) and a lower frequency of extramedullary disease (p<0.001) in whole population and in both AML1–3 and AML 4–5 subgroups. We report here novel findings that potentially implicate ptk7, a PCP gene, in hematopoiesis and AML. In vitro, we showed that ectopic expression of PTK7 promotes cell migration, cell survival and resistance to anthracyclin-induced apoptosis. Ongoing works are currently investigating which molecular mechanisms regulate PTK7 functions in normal and pathological situations.

scholarly journals Rho GTPase regulation of exocytosis in yeast is independent of GTP hydrolysis and polarization of the exocyst complex

2005 ◽  
Vol 170 (4) ◽  
pp. 583-594 ◽  
Author(s):  
Olivier Roumanie ◽  
Hao Wu ◽  
Jeffrey N. Molk ◽  
Guendalina Rossi ◽  
Kerry Bloom ◽  
...  
Keyword(s):  
Cell Surface ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Eukaryotic Cells ◽  
Secretory Vesicles ◽  
Polarized Growth ◽  
Gtp Hydrolysis ◽  
Exocyst Complex ◽  
Polarized Exocytosis

Rho GTPases are important regulators of polarity in eukaryotic cells. In yeast they are involved in regulating the docking and fusion of secretory vesicles with the cell surface. Our analysis of a Rho3 mutant that is unable to interact with the Exo70 subunit of the exocyst reveals a normal polarization of the exocyst complex as well as other polarity markers. We also find that there is no redundancy between the Rho3–Exo70 and Rho1–Sec3 pathways in the localization of the exocyst. This suggests that Rho3 and Cdc42 act to polarize exocytosis by activating the exocytic machinery at the membrane without the need to first recruit it to sites of polarized growth. Consistent with this model, we find that the ability of Rho3 and Cdc42 to hydrolyze GTP is not required for their role in secretion. Moreover, our analysis of the Sec3 subunit of the exocyst suggests that polarization of the exocyst may be a consequence rather than a cause of polarized exocytosis.

scholarly journals Novel Rho GTPase Involved in Cytokinesis and Cell Wall Integrity in the Fission Yeast Schizosaccharomyces pombe

2003 ◽  
Vol 2 (3) ◽  
pp. 521-533 ◽  
Author(s):  
Beatriz Santos ◽  
Javier Gutiérrez ◽  
Teresa M. Calonge ◽  
Pilar Pérez
Keyword(s):  
Cell Wall ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Cell Wall Integrity ◽  
Glucan Synthase ◽  
Actin Organization ◽  
Morphological Defects

ABSTRACT The Rho family of GTPases is present in all eukaryotic cells from yeast to mammals; they are regulators in signaling pathways that control actin organization and morphogenetic processes. In yeast, Rho GTPases are implicated in cell polarity processes and cell wall biosynthesis. It is known that Rho1 and Rho2 are key proteins in the construction of the cell wall, an essential structure that in Schizosaccharomyces pombe is composed of β-glucan, α-glucan, and mannoproteins. Rho1 regulates the synthesis of 1,3-β-d-glucan by activation of the 1,3-β-d-glucan synthase, and Rho2 regulates the synthesis of α-glucan by the 1,3-α-d-glucan synthase Mok1. Here we describe the characterization of another Rho GTPase in fission yeast, Rho4. rho4Δ cells are viable but display cell separation defects at high temperature. In agreement with this observation, Rho4 localizes to the septum. Overexpression of rho4 + causes lysis and morphological defects. Several lines of evidence indicate that both rho4 + deletion or rho4 + overexpression result in a defective cell wall, suggesting an additional role for Rho4 in cell wall integrity. rho4Δ cells also accumulate secretory vesicles around the septum and are defective in actin polarization. We propose that Rho4 could be involved in the regulation of the septum degradation during cytokinesis.

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