scholarly journals The NDR Kinase Cbk1 Downregulates the Transcriptional Repressor Nrg1 through the mRNA-Binding Protein Ssd1 in Candida albicans

2015 ◽  
Vol 14 (7) ◽  
pp. 671-683 ◽  
Author(s):  
Hye-Jeong Lee ◽  
Jong-Myeong Kim ◽  
Woo Kyu Kang ◽  
Heebum Yang ◽  
Jeong-Yoon Kim
Keyword(s):  
Candida Albicans ◽  
Binding Protein ◽  
Transcriptional Repressor ◽  
Hyphal Growth ◽  
Content Type ◽  
Hyphal Morphogenesis ◽  
Essential Components ◽  
Mrna Binding Protein ◽  
Mrna Binding ◽  
Ndr Kinase

ABSTRACT NDR (nuclear Dbf2-related) kinases are essential components for polarized morphogenesis, cytokinesis, cell proliferation, and apoptosis. The NDR kinase Cbk1 is required for the hyphal growth of Candida albicans ; however, the molecular functions of Cbk1 in hyphal morphogenesis are largely unknown. Here, we report that Cbk1 downregulates the transcriptional repressor Nrg1 through the mRNA-binding protein Ssd1, which has nine Cbk1 phosphorylation consensus motifs. We found that deletion of SSD1 partially suppressed the defective hyphal growth of the C. albicans cbk1 Δ/Δ mutant and that Ssd1 physically interacts with Cbk1. Cbk1 was required for Ssd1 localization to polarized growth sites. The phosphomimetic SSD1 allele ( ssd1-9E ) allowed the cbk1 Δ/Δ mutant to form short hyphae, and the phosphodeficient SSD1 allele ( ssd1-9A ) resulted in shorter hyphae than did the wild-type SSD1 allele, indicating that Ssd1 phosphorylation by Cbk1 is important for hyphal morphogenesis. Furthermore, we show that the transcriptional repressor Nrg1 does not disappear during hyphal initiation in the cbk1 Δ/Δ mutant but is completely absent in the cbk1 Δ/Δ ssd1 Δ/Δ double mutant. Deletion of SSD1 also increased Als3 expression and internalization of the cbk1 Δ/Δ mutant in the human embryonic kidney cell line HEK293T. Collectively, our results suggest that one of the functions of Cbk1 in the hyphal morphogenesis of C. albicans is to downregulate Nrg1 through Ssd1.

scholarly journals A Candida albicans Temperature-Sensitivecdc12-6Mutant Identifies Roles for Septins in Selection of Sites of Germ Tube Formation and Hyphal Morphogenesis

2012 ◽  
Vol 11 (10) ◽  
pp. 1210-1218 ◽  
Author(s):  
Lifang Li ◽  
Chengda Zhang ◽  
James B. Konopka
Keyword(s):  
Candida Albicans ◽  
Germ Tube ◽  
Leading Edge ◽  
Hyphal Growth ◽  
Striking Difference ◽  
Temperature Sensitive ◽  
Content Type ◽  
Hyphal Morphogenesis ◽  
Germ Tubes ◽  
Selection Of

ABSTRACTSeptins were identified for their role in septation inSaccharomyces cerevisiaeand were subsequently implicated in other morphogenic processes. To study septins inCandida albicanshyphal morphogenesis, a temperature-sensitive mutation was created that altered the C terminus of the essential Cdc12 septin. Thecdc12-6cells grew well at room temperature, but at 37°C they displayed expected defects in septation, nuclear localization, and bud morphogenesis. Although serum stimulated thecdc12-6cells at 37°C to form germ tube outgrowths, the mutant could not maintain polarized hyphal growth and instead formed chains of elongated cell compartments. Serum also stimulated thecdc12-6mutant to induce a hyphal reporter gene (HWP1-GFP) and a characteristic zone of filipin staining at the leading edge of growth. Interestingly,cdc12-6cells shifted to 37°C in the absence of serum gradually displayed enriched filipin staining at the tip, which may be due to the altered cell cycle regulation. A striking difference from the wild type was that thecdc12-6cells frequently formed a second germ tube in close proximity to the first. The mutant cells also failed to form the diffuse band of septins at the base of germ tubes and hyphae, indicating that this septin band plays a role in preventing proximal formation of germ tubes in a manner analogous to bud site selection. These studies demonstrate that not only are septins important for cytokinesis, but they also promote polarized morphogenesis and selection of germ tube sites that may help disseminate an infection in host tissues.

scholarly journals Phosphorylation and Proteasome Recognition of the mRNA-Binding Protein Cth2 Facilitates Yeast Adaptation to Iron Deficiency

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Antonia M. Romero ◽  
Mar Martínez-Pastor ◽  
Gang Du ◽  
Carme Solé ◽  
María Carlos ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Iron Deficiency ◽  
Metabolic Pathways ◽  
Binding Protein ◽  
Cellular Metabolism ◽  
Iron Depletion ◽  
Content Type ◽  
Amino Terminal ◽  
Mrna Binding Protein ◽  
Mrna Binding

ABSTRACT Iron is an indispensable micronutrient for all eukaryotic organisms due to its participation as a redox cofactor in many metabolic pathways. Iron imbalance leads to the most frequent human nutritional deficiency in the world. Adaptation to iron limitation requires a global reorganization of the cellular metabolism directed to prioritize iron utilization for essential processes. In response to iron scarcity, the conserved Saccharomyces cerevisiae mRNA-binding protein Cth2, which belongs to the tristetraprolin family of tandem zinc finger proteins, coordinates a global remodeling of the cellular metabolism by promoting the degradation of multiple mRNAs encoding highly iron-consuming proteins. In this work, we identify a critical mechanism for the degradation of Cth2 protein during the adaptation to iron deficiency. Phosphorylation of a patch of Cth2 serine residues within its amino-terminal region facilitates recognition by the SCFGrr1 ubiquitin ligase complex, accelerating Cth2 turnover by the proteasome. When Cth2 degradation is impaired by either mutagenesis of the Cth2 serine residues or deletion of GRR1, the levels of Cth2 rise and abrogate growth in iron-depleted conditions. Finally, we uncover that the casein kinase Hrr25 phosphorylates and promotes Cth2 destabilization. These results reveal a sophisticated posttranslational regulatory pathway necessary for the adaptation to iron depletion. IMPORTANCE Iron is a vital element for many metabolic pathways, including the synthesis of DNA and proteins, and the generation of energy via oxidative phosphorylation. Therefore, living organisms have developed tightly controlled mechanisms to properly distribute iron, since imbalances lead to nutritional deficiencies, multiple diseases, and vulnerability against pathogens. Saccharomyces cerevisiae Cth2 is a conserved mRNA-binding protein that coordinates a global reprogramming of iron metabolism in response to iron deficiency in order to optimize its utilization. Here we report that the phosphorylation of Cth2 at specific serine residues is essential to regulate the stability of the protein and adaptation to iron depletion. We identify the kinase and ubiquitination machinery implicated in this process to establish a posttranscriptional regulatory model. These results and recent findings for both mammals and plants reinforce the privileged position of E3 ubiquitin ligases and phosphorylation events in the regulation of eukaryotic iron homeostasis.

scholarly journals Hypoxia up-regulates the activity of a novel erythropoietin mRNA binding protein.

1991 ◽  
Vol 266 (25) ◽  
pp. 16594-16598
Author(s):  
I.J. Rondon ◽  
L.A. MacMillan ◽  
B.S. Beckman ◽  
M.A. Goldberg ◽  
T. Schneider ◽  
...  
Keyword(s):  
Binding Protein ◽  
Mrna Binding Protein ◽  
Mrna Binding

scholarly journals Cell Wall-Related Bionumbers and Bioestimates of Saccharomyces cerevisiae and Candida albicans

2013 ◽  
Vol 13 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Frans M. Klis ◽  
Chris G. de Koster ◽  
Stanley Brul
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Size ◽  
Pathogenic Fungus ◽  
Turgor Pressure ◽  
Hyphal Growth ◽  
Biological Research ◽  
Content Type ◽  
Starting Point

ABSTRACTBionumbers and bioestimates are valuable tools in biological research. Here we focus on cell wall-related bionumbers and bioestimates of the budding yeastSaccharomyces cerevisiaeand the polymorphic, pathogenic fungusCandida albicans. We discuss the linear relationship between cell size and cell ploidy, the correlation between cell size and specific growth rate, the effect of turgor pressure on cell size, and the reason why using fixed cells for measuring cellular dimensions can result in serious underestimation ofin vivovalues. We further consider the evidence that individual buds and hyphae grow linearly and that exponential growth of the population results from regular formation of new daughter cells and regular hyphal branching. Our calculations show that hyphal growth allowsC. albicansto cover much larger distances per unit of time than the yeast mode of growth and that this is accompanied by strongly increased surface expansion rates. We therefore predict that the transcript levels of genes involved in wall formation increase during hyphal growth. Interestingly, wall proteins and polysaccharides seem barely, if at all, subject to turnover and replacement. A general lesson is how strongly most bionumbers and bioestimates depend on environmental conditions and genetic background, thus reemphasizing the importance of well-defined and carefully chosen culture conditions and experimental approaches. Finally, we propose that the numbers and estimates described here offer a solid starting point for similar studies of other cell compartments and other yeast species.

Increased expression of the MBP mRNA binding protein HnRNP A2 during oligodendrocyte differentiation

2004 ◽  
Vol 75 (5) ◽  
pp. 614-623 ◽  
Author(s):  
M. Maggipinto ◽  
C. Rabiner ◽  
G.J. Kidd ◽  
A.J. Hawkins ◽  
R. Smith ◽  
...  
Keyword(s):  
Binding Protein ◽  
Oligodendrocyte Differentiation ◽  
Mrna Binding Protein ◽  
Mrna Binding
Sign in / Sign up

Export Citation Format

Share Document