scholarly journals A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth

2012 ◽  
Vol 198 (4) ◽  
pp. 711-730 ◽  
Author(s):  
Aurélia Vernay ◽  
Sébastien Schaub ◽  
Isabelle Guillas ◽  
Martine Bassilana ◽  
Robert A. Arkowitz
Keyword(s):  
Long Range ◽  
Membrane Lipids ◽  
Pathogenic Fungus ◽  
Filamentous Growth ◽  
Asymmetric Distribution ◽  
Cell Morphogenesis ◽  
Membrane Diffusion ◽  
Cellular Processes ◽  
Human Pathogenic Fungus

Membrane lipids have been implicated in many critical cellular processes, yet little is known about the role of asymmetric lipid distribution in cell morphogenesis. The phosphoinositide bis-phosphate PI(4,5)P2 is essential for polarized growth in a range of organisms. Although an asymmetric distribution of this phospholipid has been observed in some cells, long-range gradients of PI(4,5)P2 have not been observed. Here, we show that in the human pathogenic fungus Candida albicans a steep, long-range gradient of PI(4,5)P2 occurs concomitant with emergence of the hyphal filament. Both sufficient PI(4)P synthesis and the actin cytoskeleton are necessary for this steep PI(4,5)P2 gradient. In contrast, neither microtubules nor asymmetrically localized mRNAs are critical. Our results indicate that a gradient of PI(4,5)P2, crucial for filamentous growth, is generated and maintained by the filament tip–localized PI(4)P-5-kinase Mss4 and clearing of this lipid at the back of the cell. Furthermore, we propose that slow membrane diffusion of PI(4,5)P2 contributes to the maintenance of such a gradient.

scholarly journals Flotillin-dependent lipid-raft microdomains are required for functional phagolysosomes against fungal infections

2019 ◽  
Author(s):  
Franziska Schmidt ◽  
Andreas Thywißen ◽  
Marie Röcker ◽  
Cristina Cunha ◽  
Zoltán Cseresnyés ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Lipid Raft ◽  
Fungal Infections ◽  
Pathogenic Fungus ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Essential Components ◽  
Human Pathogenic Fungus ◽  
Lipid Raft Microdomains

SUMMARYLipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid raft microdomains are essential components of the phagolysosomal membrane of macrophages. Genetic deletion of the lipidraft chaperons flotillin-1 and flotillin-2 demonstrate that the assembly of both major defense complexes vATPase and NADPH oxidase on the phagolysosomal membrane requires lipid rafts. Furthermore, we discovered a new virulence mechanism leading to the dysregulation of lipid-raft formation by melanized wild-type conidia of the important human-pathogenic fungusAspergillus fumigatus. This results in reduced phagolysosomal acidification. Phagolysosomes with ingested melanized conidia contain a reduced amount of free Ca2+ions as compared to phagolysosomes with melanin-free conidia. In agreement with a role of Ca2+for generation of functional lipid rafts, we show that Ca2+-dependent calmodulin activity is required for lipid-raft formation on the phagolysosome. We identified a single nucleotide polymorphism in the humanFLOT1gene that results in heightened susceptibility for invasive aspergillosis in hematopoietic stem-cell transplant recipients. Collectively, flotillin-dependent lipid rafts on the phagolysosomal membrane play an essential role in protective antifungal immunity in humans.

scholarly journals Phosphatidylinositol-4-phosphate-dependent membrane traffic is critical for fungal filamentous growth

2015 ◽  
Vol 112 (28) ◽  
pp. 8644-8649 ◽  
Author(s):  
Vikram Ghugtyal ◽  
Rocio Garcia-Rodas ◽  
Agnese Seminara ◽  
Sébastien Schaub ◽  
Martine Bassilana ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Pathogenic Fungus ◽  
Membrane Traffic ◽  
Secretory Vesicle ◽  
Filamentous Growth ◽  
Membrane Dynamics ◽  
Antifungal Drugs ◽  
Human Pathogenic Fungus ◽  
Phosphatidylinositol 4 ◽  
Morphology Changes

The phospholipid phosphatidylinositol-4-phosphate [PI(4)P], generated at the Golgi and plasma membrane, has been implicated in many processes, including membrane traffic, yet its role in cell morphology changes, such as the budding to filamentous growth transition, is unknown. We show that Golgi PI(4)P is required for such a transition in the human pathogenic fungus Candida albicans. Quantitative analyses of membrane traffic revealed that PI(4)P is required for late Golgi and secretory vesicle dynamics and targeting and, as a result, is important for the distribution of a multidrug transporter and hence sensitivity to antifungal drugs. We also observed that plasma membrane PI(4)P, which we show is functionally distinct from Golgi PI(4)P, forms a steep gradient concomitant with filamentous growth, despite uniform plasma membrane PI-4-kinase distribution. Mathematical modeling indicates that local PI(4)P generation and hydrolysis by phosphatases are crucial for this gradient. We conclude that PI(4)P-regulated membrane dynamics are critical for morphology changes.

scholarly journals Dissection of Filamentous Growth by Transposon Mutagenesis in Saccharomyces cerevisiae

Genetics ◽  
1997 ◽  
Vol 145 (3) ◽  
pp. 671-684 ◽  
Author(s):  
Hans-Ulrich Mösch ◽  
Gerald R Fink
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Signaling Pathway ◽  
Filamentous Growth ◽  
Invasive Growth ◽  
Cell Morphogenesis ◽  
Phenotypic Analysis ◽  
Cellular Processes ◽  
Evolutionarily Conserved ◽  
Mutant Strains ◽  
Bud Site

Diploid Saccharomyces cerevisiae strains starved for nitrogen undergo a developmental transition from growth as single yeast form (YF) cells to a multicellular form consisting of filaments of pseudohyphal (PH) cells. Filamentous growth is regulated by an evolutionarily conserved signaling pathway that includes the small GTP-binding proteins Ras2p and Cdc42p, the protein kinases Ste20p, Ste11p and Ste7p, and the transcription factor Ste12p. Here, we designed a genetic screen for mutant strains defective for filamentous growth (dfg) to identify novel targets of the filamentation signaling pathway, and we thereby identified 16 different genes, CDC39, STE12, TEC1, WH13, NAB1, DBR1, CDC55, SRV2, TPM1, SPA2, BNI1, DFG5, DFG9, DFG10, BUD8 and DFG16, mutations that block filamentous growth. Phenotypic analysis of dfg mutant strains genetically dissects filamentous growth into the cellular processes of signal transduction, bud site selection, cell morphogenesis and invasive growth. Epistasis tests between dfg mutant alleles and dominant activated alleles of the RAS2 and STE11 genes, RAS2Val19 and STE11-4, respectively, identify putative targets for the filamentation signaling pathway. Several of the genes described here have homologues in filamentous fungi, where they also regulate fungal development.

Role of Cdc42 dynamics in the control of fission yeast cell polarization

2013 ◽  
Vol 41 (6) ◽  
pp. 1745-1749 ◽  
Author(s):  
Maitreyi Das ◽  
Fulvia Verde
Keyword(s):  
Cell Fate ◽  
Rho Gtpase ◽  
Cellular Level ◽  
Cell Polarization ◽  
Cell Fate Determination ◽  
Cell Morphogenesis ◽  
Oscillatory Dynamics ◽  
Cellular Processes ◽  
Polarized Cell Growth

Cell polarization is fundamental to many cellular processes, including cell differentiation, cell motility and cell fate determination. A key regulatory enzyme in the control of cell morphogenesis is the conserved Rho GTPase Cdc42, which breaks symmetry via self-amplifying positive-feedback mechanisms. Additional mechanisms of control, including competition between different sites of polarized cell growth and time-delayed negative feedback, define a cellular-level system that promotes Cdc42 oscillatory dynamics and modulates activated Cdc42 intracellular distribution.

scholarly journals Role for Chitin and Chitooligomers in the Capsular Architecture of Cryptococcus neoformans

2009 ◽  
Vol 8 (10) ◽  
pp. 1543-1553 ◽  
Author(s):  
Fernanda L. Fonseca ◽  
Leonardo Nimrichter ◽  
Radames J. B. Cordero ◽  
Susana Frases ◽  
Jessica Rodrigues ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cryptococcus Neoformans ◽  
Pathogenic Fungus ◽  
Monosaccharide Composition ◽  
Altered Expression ◽  
Functional Activities ◽  
Differential Reactivity ◽  
Human Pathogenic Fungus

ABSTRACT Molecules composed of β-1,4-linked N-acetylglucosamine (GlcNAc) and deacetylated glucosamine units play key roles as surface constituents of the human pathogenic fungus Cryptococcus neoformans. GlcNAc is the monomeric unit of chitin and chitooligomers, which participate in the connection of capsular polysaccharides to the cryptococcal cell wall. In the present study, we evaluated the role of GlcNAc-containing structures in the assembly of the cryptococcal capsule. The in vivo expression of chitooligomers in C. neoformans varied depending on the infected tissue, as inferred from the differential reactivity of yeast forms to the wheat germ agglutinin (WGA) in infected brain and lungs of rats. Chromatographic and dynamic light-scattering analyses demonstrated that glucuronoxylomannan (GXM), the major cryptococcal capsular component, interacts with chitin and chitooligomers. When added to C. neoformans cultures, chitooligomers formed soluble complexes with GXM and interfered in capsular assembly, as manifested by aberrant capsules with defective connections with the cell wall and no reactivity with a monoclonal antibody to GXM. Cultivation of C. neoformans in the presence of an inhibitor of glucosamine 6-phosphate synthase resulted in altered expression of cell wall chitin. These cells formed capsules that were loosely connected to the cryptococcal wall and contained fibers with decreased diameters and altered monosaccharide composition. These results contribute to our understanding of the role played by chitin and chitooligosaccharides on the cryptococcal capsular structure, broadening the functional activities attributed to GlcNAc-containing structures in this biological system.

scholarly journals Role of the rttA gene in morphogenesis, stress response, and virulence in the human pathogenic fungus Penicillium marneffei

2014 ◽  
Vol 53 (2) ◽  
pp. 119-131 ◽  
Author(s):  
S. Suwunnakorn ◽  
C. R. Cooper ◽  
A. Kummasook ◽  
M. Pongpom ◽  
P. Vanittanakom ◽  
...  
Keyword(s):  
Stress Response ◽  
Pathogenic Fungus ◽  
Penicillium Marneffei ◽  
Human Pathogenic Fungus

scholarly journals Functional analysis of the phospholipase C gene CaPLC1 and two unusual phospholipase C genes, CaPLC2 and CaPLC3, of Candida albicans

Microbiology ◽  
2005 ◽  
Vol 151 (10) ◽  
pp. 3381-3394 ◽  
Author(s):  
Donika Kunze ◽  
Inga Melzer ◽  
Désirée Bennett ◽  
Dominique Sanglard ◽  
Donna MacCallum ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Phospholipase C ◽  
Essential Gene ◽  
Pathogenic Fungus ◽  
Systemic Infection ◽  
Cellular Processes ◽  
Solid Media ◽  
Transcriptional Pattern ◽  
Human Pathogenic Fungus ◽  
Hyphal Formation

Phospholipases C are known to be important regulators of cellular processes but may also act as virulence factors of pathogenic microbes. At least three genes in the genome of the human-pathogenic fungus Candida albicans encode phospholipases with conserved phospholipase C (Plc) motifs. None of the deduced protein sequences contain N-terminal signal peptides, suggesting that these phospholipases are not secreted. In contrast to its orthologue in Sacharomyces cerevisiae, CaPLC1 seems to be an essential gene. However, a conditional mutant with reduced transcript levels of CaPLC1 had phenotypes similar to Plc1p-deficient mutants in S. cerevisiae, including reduced growth on media causing increased osmotic stress, on media with a non-glucose carbon source, or at elevated or lower temperatures, suggesting that CaPlc1p, like the Plc1p counterpart in S. cerevisiae, may be involved in multiple cellular processes. Furthermore, phenotypic screening of the heterozygous ΔCaplc1/CaPLC1 mutant showed additional defects in hyphal formation. The loss of CaPLC1 cannot be compensated by two additional PLC genes of C. albicans (CaPLC2 and CaPLC3) encoding two almost identical phospholipases C with no counterpart in S. cerevisiae but containing structural elements found in bacterial phospholipases C. Although the promoter sequences of CaPLC2 and CaPLC3 differed dramatically, the transcriptional pattern of both genes was similar. In contrast to CaPLC1, CaPLC2 and CaPLC3 are not essential. Although Caplc2/3 mutants had reduced abilities to produce hyphae on solid media, these mutants were as virulent as the wild-type in a model of systemic infection. These data suggest that C. albicans contains two different classes of phospholipases C which are involved in cellular processes but which have no specific functions in pathogenicity.

scholarly journals Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Raghavendra Pralhada Rao ◽  
Nanditha Vaidyanathan ◽  
Mathiyazhagan Rengasamy ◽  
Anup Mammen Oommen ◽  
Neeti Somaiya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Expression Pattern ◽  
Metabolic Pathway ◽  
Membrane Lipids ◽  
Gene Expression Pattern ◽  
Bioactive Molecules ◽  
Cellular Processes ◽  
Key Players

Sphingolipids, a family of membrane lipids, are bioactive molecules that participate in diverse functions controlling fundamental cellular processes such as cell division, differentiation, and cell death. Given that most of these cellular processes form the basis for several pathologies, it is not surprising that sphingolipids are key players in several pathological processes. This review discusses the role of the sphingolipid metabolic pathway in diabetes, Alzheimer’s disease, and hepatocellular carcinoma, with a special emphasis on the changes in gene expression pattern in these disease conditions. For convenience, the sphingolipid metabolic pathway is divided into hypothetical compartments (modules) with each compartment representing a physiological process and changes in gene expression pattern are mapped to each of these modules. It appears that alterations in the gene expression pattern in these disease conditions are biased to manipulate the system in order to result in a particular disease.

scholarly journals Vesicle-associated melanization in Cryptococcus neoformans

Microbiology ◽  
2009 ◽  
Vol 155 (12) ◽  
pp. 3860-3867 ◽  
Author(s):  
Helene C. Eisenman ◽  
Susana Frases ◽  
André M. Nicola ◽  
Marcio L. Rodrigues ◽  
Arturo Casadevall
Keyword(s):  
Cell Wall ◽  
Cryptococcus Neoformans ◽  
Extracellular Vesicles ◽  
Lipid A ◽  
Pathogenic Fungus ◽  
Pathogenic Fungi ◽  
Spherical Particles ◽  
Human Pathogenic Fungus ◽  
Kinetics Of

Recently, several pathogenic fungi were shown to produce extracellular vesicles that contain various components associated with virulence. In the human pathogenic fungus Cryptococcus neoformans, these components included laccase, an enzyme that catalyses melanin synthesis. Spherical melanin granules have been observed in the cell wall of C. neoformans. Given that melanin granules have dimensions that are comparable to those of extracellular vesicles, and that metazoan organisms produce melanin in vesicular structures known as melanosomes, we investigated the role of vesicles in cryptococcal melanization. Extracellular vesicles melanized when incubated with the melanin precursor l-3,4-dihydroxyphenylalanine (l-DOPA). The kinetics of substrate incorporation into cells and vesicles was analysed using radiolabelled l-DOPA. The results indicated that substrate incorporation was different for cells and isolated vesicles. Acid-generated melanin ghosts stained with lipophilic dyes, implying the presence of associated lipid. A model for C. neoformans melanization is proposed that accounts for these observations and provides a mechanism for the assembly of melanin into relatively uniform spherical particles stacked in an orderly arrangement in the cell wall.

The Role of Technological Change in the Long-run Global Economy Forecasting

2013 ◽  
pp. 97-116 ◽  
Author(s):  
A. Apokin
Keyword(s):  
Technological Change ◽  
Data Quality ◽  
Long Range ◽  
Global Economy ◽  
World Economy ◽  
Qualitative Approaches ◽  
Long Run ◽  
The World ◽  
National Economies

The author compares several quantitative and qualitative approaches to forecasting to find appropriate methods to incorporate technological change in long-range forecasts of the world economy. A?number of long-run forecasts (with horizons over 10 years) for the world economy and national economies is reviewed to outline advantages and drawbacks for different ways to account for technological change. Various approaches based on their sensitivity to data quality and robustness to model misspecifications are compared and recommendations are offered on the choice of appropriate technique in long-run forecasts of the world economy in the presence of technological change.

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