Movement of yeast 1,3‐β‐glucan synthase is essential for uniform cell wall synthesis

Utsugi, Takahiko; Minemura, Masayo; Hirata, Aiko; Abe, Mitsuhiro; Watanabe, Dai; Ohya, Yoshikazu

doi:10.1046/j.1356-9597.2001.00495.x

Cited by 89 publications

(66 citation statements)

References 42 publications

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“…Other factors affect ␤-1,3-glucan synthesis by regulation of the catalytic subunit of GS. Movement of Fks1p driven by actin is required for the construction of a uniform and solid cell wall (Utsugi et al, 2002). Transcription of FKS2 is up-regulated in response to cell wall stress induced by heat, cell wall mutations, and cell wall-perturbing agents (Zhao et al, 1998;de Nobel et al, 2000;Lagorce et al, 2003;Garcia et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Zhong

Gvozdenović-Jeremić

Webster

et al. 2005

MBoC

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Disruption of PGS1, which encodes the enzyme that catalyzes the committed step of cardiolipin (CL) synthesis, results in loss of the mitochondrial anionic phospholipids phosphatidylglycerol (PG) and CL. The pgs1⌬ mutant exhibits severe growth defects at 37°C. To understand the essential functions of mitochondrial anionic lipids at elevated temperatures, we isolated suppressors of pgs1⌬ that grew at 37°C. One of the suppressors has a loss of function mutation in KRE5, which is involved in cell wall biogenesis. The cell wall of pgs1⌬ contained markedly reduced ␤-1,3-glucan, which was restored in the suppressor. Stabilization of the cell wall with osmotic support alleviated the cell wall defects of pgs1⌬ and suppressed the temperature sensitivity of all CL-deficient mutants. Evidence is presented suggesting that the previously reported inability of pgs1⌬ to grow in the presence of ethidium bromide was due to defective cell wall integrity, not from "petite lethality." These findings demonstrated that mitochondrial anionic lipids are required for cellular functions that are essential in cell wall biogenesis, the maintenance of cell integrity, and survival at elevated temperature. INTRODUCTIONCardiolipin (CL), a unique anionic phospholipid with dimeric structure, is ubiquitous in eukaryotes and primarily found in the mitochondrial inner membrane . CL plays a key role in mitochondrial bioenergetics (Jiang et al., 2000; Greenberg, 2000, 2002;Schlame et al., 2000;Pfeiffer et al., 2003) and is also involved in mitochondrial biogenesis (Kawasaki et al., 1999;Jiang et al., 2000). Defective remodeling of CL is associated with Barth syndrome, a severe genetic disorder characterized by cardiomyopathy, neutropenia, skeletal myopathy, and respiratory chain defects (Vreken et al., 2000). The phenotype of Barth syndrome is dependent upon multiple factors that are not well understood (Barth et al., 1983(Barth et al., , 1996. Elucidation of the functions of CL will help to clarify the abnormalities associated with this disorder.The biosynthesis of CL is conserved in eukaryotic organisms. It occurs via three enzymatic reactions , including formation of phosphatidylglycerolphosphate (PGP) from CDP-DAG and glycerol-3-P, dephosphorylation of PGP to phosphatidylglycerol (PG), and condensation of CDP-DAG and PG to form CL. Disruption of PGS1, the structural gene encoding PGP synthase, results in the complete loss of both PG and CL (Janitor et al., 1996;Chang et al., 1998a). The crd1⌬ mutant, which lacks CL synthase, has no detectable CL but accumulates PG (Jiang et al., 1997;Chang et al., 1998b;Tuller et al., 1998;Jiang et al., 2000;Pfeiffer et al., 2003;Zhong et al., 2004). The human taffazin gene (TAZ1), which is associated with Barth syndrome, encodes a transacylase that may be involved in the remodeling of CL (Xu et al., 2003). Deletion of the yeast homolog of this gene, TAZ1, leads to decreased CL, aberrant CL acyl species, and accumulation of monolysocardiolipin . Mutants deficient in CL biosynthesis exhibit growth defects at elevat...

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Section: Discussionmentioning

confidence: 99%

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Zhong

Gvozdenović-Jeremić

Webster

et al. 2005

MBoC

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“…1). Furthermore, Fks1, the presumptive catalytic subunit of the glucan synthase complex is co-localized within cortical actin patches where it moves on the cell surface to sites of cell wall remodeling (Utsugi et al, 2002).…”

Section: Role Of Cell Wall Biosynthesis and Integrity Pathways In Drumentioning

confidence: 99%

Resistance to echinocandin-class antifungal drugs

Perlin¹

2007

Drug Resistance Updates

455

400

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Invasive fungal infections cause morbidity and mortality in severely ill patients, and limited drug classes restrict treatment choices. The echinocandins drugs are the first new class of antifungal compounds that target the fungal cell wall by blocking β-1,3-D-glucan synthase. Elevated MIC values with occasional treatment failure have been reported for strains of Candida. Yet, an uncertain correlation exists between clinical failure and elevated MIC values for the echinocandin drugs. Fungi display several adaptive physiological mechanisms that result in elevated MIC values. However, resistance to echinocandin drugs among clinical isolates is associated with amino acid substitutions in two "hot-spot" regions of Fks1, the major subunit of glucan synthase. The mutations, yielding highly elevated MIC values, are genetically dominant and confer cross-resistance to all echinocandin drugs. Prominent Fks1 mutations decrease the sensitivity of glucan synthase for drug by one thousand-fold or more, and strains harboring such mutations may require a concomitant increase in drug to reduce fungal organ burdens in animal infection models. The Fks1-mediated resistance mechanism is conserved in a wide variety of Candida spp. and can account for intrinsic reduced susceptibility of certain species. Fks1 mutations confer resistance in both yeasts and moulds suggesting that this mechanism is pervasive in the fungal kingdom.

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“…For example, mutations in both FKS1 and FKS2 result in lowered b1,6-glucan synthesis (Dijkgraaf et al 2002). Fks1 is localized to the plasma membrane at sites of polarized growth and cell wall remodeling throughout the cell cycle, and this localization coincides with that of actin patches (Qadota et al 1996;Dijkgraaf et al 2002;Utsugi et al 2002). Fks1 transits the secretory pathway because it accumulates intracellularly in vesicular transport mutants and its activity is sensitive to phytosphingosine levels in the ER (El-Sherbeini and Clemas 1995; Abe et al 2001;File S7).…”

Section: Biosynthesis Of Wall Components At the Plasma Membranementioning

confidence: 99%

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

2012

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The wall gives a Saccharomyces cerevisiae cell its osmotic integrity; defines cell shape during budding growth, mating, sporulation, and pseudohypha formation; and presents adhesive glycoproteins to other yeast cells. The wall consists of b1,3-and b1,6-glucans, a small amount of chitin, and many different proteins that may bear N-and O-linked glycans and a glycolipid anchor. These components become cross-linked in various ways to form higher-order complexes. Wall composition and degree of cross-linking vary during growth and development and change in response to cell wall stress. This article reviews wall biogenesis in vegetative cells, covering the structure of wall components and how they are cross-linked; the biosynthesis of N-and O-linked glycans, glycosylphosphatidylinositol membrane anchors, b1,3-and b1,6-linked glucans, and chitin; the reactions that cross-link wall components; and the possible functions of enzymatic and nonenzymatic cell wall proteins. TABLE OF CONTENTS Abstract 775Introduction 777

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Movement of yeast 1,3‐β‐glucan synthase is essential for uniform cell wall synthesis

Cited by 89 publications

References 42 publications

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Loss of Function ofKRE5Suppresses Temperature Sensitivity of Mutants Lacking Mitochondrial Anionic Lipids

Resistance to echinocandin-class antifungal drugs

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

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