scholarly journals The Candida albicans GAP Gene Family Encodes Permeases Involved in General and Specific Amino Acid Uptake and Sensing

2011 ◽  
Vol 10 (9) ◽  
pp. 1219-1229 ◽  
Author(s):  
Lucie Kraidlova ◽  
Griet Van Zeebroeck ◽  
Patrick Van Dijck ◽  
Hana Sychrová
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Signal Transduction Pathway ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Content Type ◽  
Six Genes

ABSTRACTTheSaccharomyces cerevisiaegeneral amino acid permease Gap1 (ScGap1) not only mediates the uptake of most amino acids but also functions as a receptor for the activation of protein kinase A (PKA). Fungal pathogens can colonize different niches in the host, each containing various levels of different amino acids and sugars. TheCandida albicansgenome contains six genes homologous to theS. cerevisiae GAP1. The expression of these six genes inS. cerevisiaeshowed that the products of all sixC. albicansgenes differ in their transport capacities.C. albicansGap2 (CaGap2) is the true orthologue ofScGap1 as it transports all tested amino acids. The otherCaGap proteins have narrower substrate specificities thoughCaGap1 andCaGap6 transport several structurally unrelated amino acids.CaGap1,CaGap2, andCaGap6 also function as sensors. Upon detecting some amino acids, e.g., methionine, they are involved in a rapid activation of trehalase, a downstream target of PKA. Our data show thatCaGAPgenes can be functionally expressed inS. cerevisiaeand thatCaGap permeases communicate to the intracellular signal transduction pathway similarly toScGap1.

scholarly journals Amino Acid Sensing and Assimilation by the Fungal Pathogen Candida albicans in the Human Host

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Fitz Gerald S. Silao ◽  
Per O. Ljungdahl
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Close Association ◽  
Amino Acid Uptake ◽  
Nutrient Sensing ◽  
Acid Uptake ◽  
Uptake And Metabolism

Nutrient uptake is essential for cellular life and the capacity to perceive extracellular nutrients is critical for coordinating their uptake and metabolism. Commensal fungal pathogens, e.g., Candida albicans, have evolved in close association with human hosts and are well-adapted to using diverse nutrients found in discrete host niches. Human cells that cannot synthesize all amino acids require the uptake of the “essential amino acids” to remain viable. Consistently, high levels of amino acids circulate in the blood. Host proteins are rich sources of amino acids but their use depends on proteases to cleave them into smaller peptides and free amino acids. C. albicans responds to extracellular amino acids by pleiotropically enhancing their uptake and derive energy from their catabolism to power opportunistic virulent growth. Studies using Saccharomyces cerevisiae have established paradigms to understand metabolic processes in C. albicans; however, fundamental differences exist. The advent of CRISPR/Cas9-based methods facilitate genetic analysis in C. albicans, and state-of-the-art molecular biological techniques are being applied to directly examine growth requirements in vivo and in situ in infected hosts. The combination of divergent approaches can illuminate the biological roles of individual cellular components. Here we discuss recent findings regarding nutrient sensing with a focus on amino acid uptake and metabolism, processes that underlie the virulence of C. albicans.

scholarly journals Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

2013 ◽  
Vol 34 (5) ◽  
pp. 794-806 ◽  
Author(s):  
Dana Laor ◽  
Adiel Cohen ◽  
Metsada Pasmanik-Chor ◽  
Varda Oron-Karni ◽  
Martin Kupiec ◽  
...  
Keyword(s):  
Amino Acid ◽  
Transcript Level ◽  
Amino Acid Uptake ◽  
Cellular Growth ◽  
Acid Uptake ◽  
Tor Signaling ◽  
Amino Acid Permease ◽  
Content Type ◽  
The Family ◽  
Nitrogen Conditions

TOR proteins reside in two distinct complexes, TOR complexes 1 and 2 (TORC1 and TORC2), that are central for the regulation of cellular growth, proliferation, and survival. TOR is also the target for the immunosuppressive and anticancer drug rapamycin. InSchizosaccharomyces pombe, disruption of the TSC complex, mutations in which can lead to the tuberous sclerosis syndrome in humans, results in a rapamycin-sensitive phenotype under poor nitrogen conditions. We show here that the sensitivity to rapamycin is mediated via inhibition of TORC1 and suppressed by overexpression ofisp7+, a member of the family of 2-oxoglutarate-Fe(II)-dependent oxygenase genes. The transcript level ofisp7+is negatively regulated by TORC1 but positively regulated by TORC2. Yet we find extensive similarity between the transcriptome of cells disrupted forisp7+and cells mutated in the catalytic subunit of TORC1. Moreover, Isp7 regulates amino acid permease expression in a fashion similar to that of TORC1 and opposite that of TORC2. Overexpression ofisp7+induces TORC1-dependent phosphorylation of ribosomal protein Rps6 while inhibiting TORC2-dependent phosphorylation and activation of the AGC-like kinase Gad8. Taken together, our findings suggest a central role for Isp7 in amino acid homeostasis and the presence ofisp7+-dependent regulatory loops that affect both TORC1 and TORC2.

scholarly journals The Fungal Pathogen Candida albicans Autoinduces Hyphal Morphogenesis by Raising Extracellular pH

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Slavena Vylkova ◽  
Aaron J. Carman ◽  
Heather A. Danhof ◽  
John R. Collette ◽  
Huaijin Zhou ◽  
...  
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Carbon Source ◽  
Fungal Pathogen ◽  
Host Cells ◽  
Acid Uptake ◽  
Content Type ◽  
Virulence Trait ◽  
Ph Adaptation

ABSTRACTpH homeostasis is critical for all organisms; in the fungal pathogenCandida albicans, pH adaptation is critical for virulence in distinct host niches. We demonstrate that beyond adaptation,C. albicansactively neutralizes the environment from either acidic or alkaline pHs. Under acidic conditions, this species can raise the pH from 4 to >7 in less than 12 h, resulting in autoinduction of the yeast-hyphal transition, a critical virulence trait. Extracellular alkalinization has been reported to occur in several fungal species, but under the specific conditions that we describe, the phenomenon is more rapid than previously observed. Alkalinization is linked to carbon deprivation, as it occurs in glucose-poor media and requires exogenous amino acids. These conditions are similar to those predicted to exist inside phagocytic cells, and we find a strong correlation between the use of amino acids as a cellular carbon source and the degree of alkalinization. Genetic and genomic approaches indicate an emphasis on amino acid uptake and catabolism in alkalinizing cells. Mutations in four genes,STP2, a transcription factor regulating amino acid permeases,ACH1(acetyl-coenzyme A [acetyl-CoA] hydrolase),DUR1,2(urea amidolyase), andATO5, a putative ammonia transporter, abolish or delay neutralization. The pH changes are the result of the extrusion of ammonia, as observed in other fungi. We propose that nutrient-deprivedC. albicanscells catabolize amino acids as a carbon source, excreting the amino nitrogen as ammonia to raise environmental pH and stimulate morphogenesis, thus directly contributing to pathogenesis.IMPORTANCECandida albicansis the most important fungal pathogen of humans, causing disease at multiple body sites. The ability to switch between multiple morphologies, including a rounded yeast cell and an elongated hyphal cell, is a key virulence trait in this species, as this reversible switch is thought to promote dissemination and tissue invasion in the host. We report here thatC. albicanscan actively alter the pH of its environment and induce its switch to the hyphal form. The change in pH is caused by the release of ammonia from the cells produced during the breakdown of amino acids. This phenomenon is unprecedented in a human pathogen and may substantially impact host physiology by linking morphogenesis, pH adaptation, carbon metabolism, and interactions with host cells, all of which are critical for the ability ofC. albicansto cause disease.

scholarly journals Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an S-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis

mSphere ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Lucie Kraidlova ◽  
Sanne Schrevens ◽  
Hélène Tournu ◽  
Griet Van Zeebroeck ◽  
Hana Sychrova ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Virulence Factor ◽  
Amino Acid Transporters ◽  
Amino Acid Permease ◽  
Content Type ◽  
Important Virulence Factor ◽  
General Amino Acid Permease

ABSTRACT Candida albicans is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the C. albicans genome encodes 6 orthologues of the Saccharomyces. cerevisiae general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that C. albicans Gap2 is the functional orthologue of ScGap1 and that C. albicans Gap4 is an orthologue of ScSam3, an S-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of C. albicans. Amino acids are key sources of nitrogen for growth of Candida albicans. In order to detect and take up these amino acids from a broad range of different and changing nitrogen sources inside the host, this fungus must be able to adapt via its expression of genes for amino acid uptake and further metabolism. We analyzed six C. albicans putative general amino acid permeases based on their homology to the Saccharomyces cerevisiae Gap1 general amino acid permease. We generated single- and multiple-deletion strains and found that, based on growth assays and transcriptional or posttranscriptional regulation, Gap2 is the functional orthologue to ScGap1, with broad substrate specificity. Expression analysis showed that expression of all GAP genes is under control of the Csy1 amino acid sensor, which is different from the situation in S. cerevisiae, where the expression of ScGAP1 is not regulated by Ssy1. We show that Gap4 is the functional orthologue of ScSam3, the only S-adenosylmethionine (SAM) transporter in S. cerevisiae, and we report that Gap4 is required for SAM-induced morphogenesis. IMPORTANCE Candida albicans is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the C. albicans genome encodes 6 orthologues of the Saccharomyces. cerevisiae general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that C. albicans Gap2 is the functional orthologue of ScGap1 and that C. albicans Gap4 is an orthologue of ScSam3, an S-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of C. albicans.

scholarly journals Candida albicans Csy1p Is a Nutrient Sensor Important for Activation of Amino Acid Uptake and Hyphal Morphogenesis

2004 ◽  
Vol 3 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Elisa Brega ◽  
Rachel Zufferey ◽  
Choukri Ben Mamoun
Keyword(s):  
Candida Albicans ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Specific Amino Acid ◽  
Primary Amino ◽  
Amino Acid Sensing ◽  
Amino Acid Sensor

ABSTRACT Candida albicans is an important human pathogen that displays a remarkable ability to detect changes in its environment and to respond appropriately by changing its cell morphology and physiology. Serum- and amino acid-based media are known to induce filamentous growth in this organism. However, the mechanism by which amino acids induce filamentation is not yet known. Here, we describe the identification and characterization of the primary amino acid sensor of C. albicans, Csy1. We show that Csy1p plays an important role in amino acid sensing and filamentation. Loss of Csy1p results in a lack of amino acid-mediated activation of amino acid transport and a lack of induction of transcription of specific amino acid permease genes. Furthermore, a csy1Δ/csy1Δ strain, lacking Csy1p, is defective in filamentation and displays altered colony morphology in serum- and amino acid-based media. These data provide the first evidence that C. albicans utilizes the amino acid sensor Csy1p to probe its environment, coordinate its nutritional requirements, and determine its morphological state.

scholarly journals Divergence of Stp1 and Stp2 Transcription Factors in Candida albicans Places Virulence Factors Required for Proper Nutrient Acquisition under Amino Acid Control

2005 ◽  
Vol 25 (21) ◽  
pp. 9435-9446 ◽  
Author(s):  
Paula Martínez ◽  
Per O. Ljungdahl
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Transcription Factors ◽  
Amino Acid ◽  
Active Form ◽  
Amino Acid Uptake ◽  
Extracellular Proteins ◽  
Proteolytic Processing ◽  
Acid Uptake ◽  
Processed Form

ABSTRACT Candida albicans possesses a plasma membrane-localized sensor of extracellular amino acids. Here, we show that in response to amino acids, this sensor induces the proteolytic processing of two latent transcription factors, Stp1 and Stp2. Processing removes negative regulatory motifs present in the N-terminal domains of these factors. Strikingly, Stp1 and Stp2 exhibit a clear dichotomy in the genes they transactivate. The shorter active form of Stp2 activates genes required for amino acid uptake. The processed form of Stp1 activates genes required for degradation of extracellular protein and uptake of peptides, and cells lacking Stp1 do not express the secreted aspartyl protease SAP2 or the oligopeptide transporter OPT1. Consequently, stp1 null mutants are unable to grow on media with protein as the sole nitrogen source. Cells expressing the STP1* allele that encodes a protein lacking the inhibitory N-terminal domain constitutively express SAP2 and OPT1 even in the absence of extracellular proteins or peptides. Also, we show that Stp1 levels, but not Stp2 levels, are downregulated in the presence of millimolar concentrations of extracellular amino acids. These results define the hierarchy of regulatory mechanisms that differentially control two discrete pathways for the assimilation of nitrogen.

scholarly journals The amino acid transporter AAP1 mediates growth and grain yield by regulating neutral amino acid uptake and reallocation in Oryza sativa

2020 ◽  
Vol 71 (16) ◽  
pp. 4763-4777 ◽  
Author(s):  
Yuanyuan Ji ◽  
Weiting Huang ◽  
Bowen Wu ◽  
Zhongming Fang ◽  
Xuelu Wang
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Grain Yield ◽  
Amino Acid Uptake ◽  
Neutral Amino Acid ◽  
Organic N ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Short Palindromic Repeat ◽  
Exogenous Treatment

Abstract Nitrogen (N) is a major element necessary for crop yield. In most plants, organic N is primarily transported in the form of amino acids. Here, we show that amino acid permease 1 (AAP1) functions as a positive regulator of growth and grain yield in rice. We found that the OsAAP1 gene is highly expressed in rice axillary buds, leaves, and young panicles, and that the OsAAP1 protein is localized to both the plasma membrane and the nuclear membrane. Compared with the wild-type ZH11, OsAAP1 overexpression (OE) lines exhibited increased filled grain numbers as a result of enhanced tillering, while RNAi and CRISPR (clustered regularly interspaced short palindromic repeat; Osaap1) knockout lines showed the opposite phenotype. In addition, OsAAP1-OE lines had higher concentrations of neutral and acidic amino acids, but lower concentrations of basic amino acids in the straw. An exogenous treatment with neutral amino acids promoted axillary bud outgrowth more strongly in the OE lines than in the WT, RNAi, or Osaap1 lines. Transcriptome analysis of Osaap1 further demonstrated that OsAAP1 may affect N transport and metabolism, and auxin, cytokinin, and strigolactone signaling in regulating rice tillering. Taken together, these results support that increasing neutral amino acid uptake and reallocation via OsAAP1 could improve growth and grain yield in rice.

scholarly journals Expression study of an Amino Acid Permease-like gene in Phaseolus vulgaris L.

2020 ◽  
Vol 7 (2) ◽  
pp. 251-256
Author(s):  
Nisha Patwa ◽  
Brototi Chakraborty ◽  
Jolly Basak
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Phaseolus Vulgaris ◽  
Critical Role ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Dependent Relationship ◽  
Relationship Of

Amino acid permease-like (AAP-like) gene plays a critical role in absorbing amino acids through roots in plants. A number of studies have been done on amino acids uptake in plants but till date there is no report about the expression of AAP gene in Phaseolus under field allied condition. The aim of this study is to measure the expression of AAP-like gene on alanine, glycine and proline amino acid uptake capacity in Phaseolus vulgaris at field relevant concentrations. Amongst three amino acids, a drastic significant increase of 63.15 fold in expression of AAP-like gene is observed in 50 µM alanine at 2 hr. At 50 µM of proline and 25 µM of alanine, AAP-like gene expression also shows high expression of 43.71 fold at 2 hr and 42.50 fold at 1 hr respectively. This study elucidated the dose dependent relationship of glycine, alanine and proline with the expression of AAP-like gene in amino acid transport in natural conditions in roots of P. vulgaris. Additionally, this research is also useful in identification of plants needing less surplus nitrogen additions and helpful in optimizing fertilizers by tailoring AAP gene expression to match plant uptake capacities in agriculture.

Gamma-Glutamyl-Amino Acids as Signals for the Hormonal Regulation of Amino Acid Uptake by the Mammary Gland of the Lactating Rat

Neonatology ◽  
1985 ◽  
Vol 48 (4) ◽  
pp. 250-256 ◽  
Author(s):  
Juan R. Viña ◽  
Inmaculada R. Puertes ◽  
Juan B. Montoro ◽  
Guillermo T. Saez ◽  
José Viña
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Hormonal Regulation ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Gamma Glutamyl

scholarly journals Action of growth hormone in vitro on the net uptake and incorporation into protein of amino acids in muscle from intact rabbits given protein-deficient diets

1976 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
M. R. Turner ◽  
P. J. Reeds ◽  
K. A. Munday
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
De Novo ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Incorporation ◽  
Acid Incorporation

1. Net amino acid uptake, and incorporation into protein have been measured in vitro in the presence and absence of porcine growth hormone (GH) in muscle from intact rabbits fed for 5 d on low-protein (LP), protein-free (PF) or control diets.2. In muscle from control and LP animals GH had no effect on the net amino acid uptake but stimulated amino acid incorporation into protein, although this response was less in LP animals than in control animals.3. In muscle from PF animals, GH stimulated both amino acid incorporation into protein and the net amino acid uptake, a type of response which also occurs in hypophysectomized animals. The magnitude of the effect of GH on the incorporation of amino acids into protein was reduced in muscle from PF animals.4. The effect of GH on the net amino acid uptake in PF animals was completely blocked by cycloheximide; the uptake effect of GH in these animals was dependent therefore on de novo protein synthesis.5. It is proposed that in the adult the role of growth hormone in protein metabolism is to sustain cellular protein synthesis when there is a decrease in the level of substrate amino acids, similar to that which occurs during a short-term fast or when the dietary protein intake is inadequate.

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