scholarly journals The Dissection of SNAREs Reveals Key Factors for Vesicular Trafficking to the Endosome-like Compartment and Apicoplast via the Secretory System in Toxoplasma gondii

mBio ◽  
2021 ◽  
Author(s):  
Shinuo Cao ◽  
Juan Yang ◽  
Jiawen Fu ◽  
Heming Chen ◽  
Honglin Jia
Keyword(s):  
Toxoplasma Gondii ◽  
Transport System ◽  
Vesicular Trafficking ◽  
Vesicle Transport ◽  
Key Factors ◽  
Content Type ◽  
Global View ◽  
Transport Vesicles ◽  
Secretory System

SNAREs are essential for the fusion of the transport vesicles and target membranes and, thus, provide perfect targets for obtaining a global view of the vesicle transport system. In this study, we report that a novel Qc-SNARE (TgStx19) instead of Use1p is located at the ER and acts as a partner of TgStx18 in T. gondii .

scholarly journals A Thioredoxin Family Protein of the Apicoplast Periphery Identifies Abundant Candidate Transport Vesicles in Toxoplasma gondii

2008 ◽  
Vol 7 (9) ◽  
pp. 1518-1529 ◽  
Author(s):  
Amy E. DeRocher ◽  
Isabelle Coppens ◽  
Anuradha Karnataki ◽  
Luke A. Gilbert ◽  
Michael E. Rome ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Birth Defects ◽  
Transport Proteins ◽  
Toxoplasmic Encephalitis ◽  
Transport Vesicles ◽  
Family Protein ◽  
N Terminus ◽  
Secretory System

ABSTRACT Toxoplasma gondii, which causes toxoplasmic encephalitis and birth defects, contains an essential chloroplast-related organelle to which proteins are trafficked via the secretory system. This organelle, the apicoplast, is bounded by multiple membranes. In this report we identify a novel apicoplast-associated thioredoxin family protein, ATrx1, which is predominantly soluble or peripherally associated with membranes, and which localizes primarily to the outer compartments of the organelle. As such, it represents the first protein to be identified as residing in the apicoplast intermembrane spaces. ATrx1 lacks the apicoplast targeting sequences typical of luminal proteins. However, sequences near the N terminus are required for proper targeting of ATrx1, which is proteolytically processed from a larger precursor to multiple smaller forms. This protein reveals a population of vesicles, hitherto unrecognized as being highly abundant in the cell, which may serve to transport proteins to the apicoplast.

scholarly journals Loss of the Conserved Alveolate Kinase MAPK2 Decouples Toxoplasma Cell Growth from Cell Division

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Xiaoyu Hu ◽  
William J. O’Shaughnessy ◽  
Tsebaot G. Beraki ◽  
Michael L. Reese
Keyword(s):  
Toxoplasma Gondii ◽  
Protein Kinases ◽  
Daughter Cell ◽  
Protozoan Parasite ◽  
Productive Infection ◽  
Centrosome Duplication ◽  
Loss Of Function ◽  
Content Type ◽  
Mitogen Activated Protein ◽  
Parasite Replication

ABSTRACT Mitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The apicomplexan parasite Toxoplasma gondii expresses three MAPKs. Two of these, extracellular signal-regulated kinase 7 (ERK7) and MAPKL1, have been implicated in the regulation of conoid biogenesis and centrosome duplication, respectively. The third kinase, MAPK2, is specific to and conserved throughout the Alveolata, although its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss of function in Toxoplasma. We observed that parasites lacking MAPK2 failed to duplicate their centrosomes and therefore did not initiate daughter cell budding, which ultimately led to parasite death. MAPK2-deficient parasites initiated but did not complete DNA replication and arrested prior to mitosis. Surprisingly, the parasites continued to grow and replicate their Golgi apparatus, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by the depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest that MAPK2 regulates a process at a distal site that is required for the completion of centrosome duplication and the initiation of parasite mitosis. IMPORTANCE Toxoplasma gondii is a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the developing fetus. Rapid parasite replication is critical for establishing a productive infection. Here, we demonstrate that a Toxoplasma protein kinase called MAPK2 is conserved throughout the Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, T. gondii MAPK2 (TgMAPK2) appears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to the Alveolata and not found in metazoa and likely is a critical component of an essential parasite-specific signaling network.

scholarly journals Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in Toxoplasma gondii

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Maude F. Lévêque ◽  
Laurence Berry ◽  
Michael J. Cipriano ◽  
Hoa-Mai Nguyen ◽  
Boris Striepen ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Growth Conditions ◽  
Model Organisms ◽  
Secondary Endosymbiosis ◽  
Related Protein ◽  
Content Type ◽  
Superresolution Microscopy ◽  
Animal Pathogens ◽  
Cellular Components ◽  
Catabolic Process

ABSTRACT Autophagy is a catabolic process widely conserved among eukaryotes that permits the rapid degradation of unwanted proteins and organelles through the lysosomal pathway. This mechanism involves the formation of a double-membrane structure called the autophagosome that sequesters cellular components to be degraded. To orchestrate this process, yeasts and animals rely on a conserved set of autophagy-related proteins (ATGs). Key among these factors is ATG8, a cytoplasmic protein that is recruited to nascent autophagosomal membranes upon the induction of autophagy. Toxoplasma gondii is a potentially harmful human pathogen in which only a subset of ATGs appears to be present. Although this eukaryotic parasite seems able to generate autophagosomes upon stresses such as nutrient starvation, the full functionality and biological relevance of a canonical autophagy pathway are as yet unclear. Intriguingly, in T. gondii, ATG8 localizes to the apicoplast under normal intracellular growth conditions. The apicoplast is a nonphotosynthetic plastid enclosed by four membranes resulting from a secondary endosymbiosis. Using superresolution microscopy and biochemical techniques, we show that TgATG8 localizes to the outermost membrane of this organelle. We investigated the unusual function of TgATG8 at the apicoplast by generating a conditional knockdown mutant. Depletion of TgATG8 led to rapid loss of the organelle and subsequent intracellular replication defects, indicating that the protein is essential for maintaining apicoplast homeostasis and thus for survival of the tachyzoite stage. More precisely, loss of TgATG8 led to abnormal segregation of the apicoplast into the progeny because of a loss of physical interactions of the organelle with the centrosomes. IMPORTANCE By definition, autophagy is a catabolic process that leads to the digestion and recycling of eukaryotic cellular components. The molecular machinery of autophagy was identified mainly in model organisms such as yeasts but remains poorly characterized in phylogenetically distant apicomplexan parasites. We have uncovered an unusual function for autophagy-related protein ATG8 in Toxoplasma gondii: TgATG8 is crucial for normal replication of the parasite inside its host cell. Seemingly unrelated to the catabolic autophagy process, TgATG8 associates with the outer membrane of the nonphotosynthetic plastid harbored by the parasite called the apicoplast, and there it plays an important role in the centrosome-driven inheritance of the organelle during cell division. This not only reveals an unexpected function for an autophagy-related protein but also sheds new light on the division process of an organelle that is vital to a group of important human and animal pathogens.

scholarly journals Trk2 Potassium Transport System in Streptococcus mutans and Its Role in Potassium Homeostasis, Biofilm Formation, and Stress Tolerance

2016 ◽  
Vol 198 (7) ◽  
pp. 1087-1100 ◽  
Author(s):  
Gursonika Binepal ◽  
Kamal Gill ◽  
Paula Crowley ◽  
Martha Cordova ◽  
L. Jeannine Brady ◽  
...  
Keyword(s):  
Stress Tolerance ◽  
Streptococcus Mutans ◽  
Transport System ◽  
Biofilm Formation ◽  
Cellular Response ◽  
Pathogenic Bacteria ◽  
Transport Systems ◽  
Content Type ◽  
Growth And Survival ◽  
Dental Biofilm

ABSTRACTPotassium (K+) is the most abundant cation in the fluids of dental biofilm. The biochemical and biophysical functions of K+and a variety of K+transport systems have been studied for most pathogenic bacteria but not for oral pathogens. In this study, we establish the modes of K+acquisition inStreptococcus mutansand the importance of K+homeostasis for its virulence attributes. TheS. mutansgenome harbors four putative K+transport systems that included two Trk-like transporters (designated Trk1 and Trk2), one glutamate/K+cotransporter (GlnQHMP), and a channel-like K+transport system (Kch). Mutants lacking Trk2 had significantly impaired growth, acidogenicity, aciduricity, and biofilm formation. [K+] less than 5 mM eliminated biofilm formation inS. mutans. The functionality of the Trk2 system was confirmed by complementing anEscherichia coliTK2420 mutant strain, which resulted in significant K+accumulation, improved growth, and survival under stress. Taken together, these results suggest that Trk2 is the main facet of the K+-dependent cellular response ofS. mutansto environment stresses.IMPORTANCEBiofilm formation and stress tolerance are important virulence properties of caries-causingStreptococcus mutans. To limit these properties of this bacterium, it is imperative to understand its survival mechanisms. Potassium is the most abundant cation in dental plaque, the natural environment ofS. mutans. K+is known to function in stress tolerance, and bacteria have specialized mechanisms for its uptake. However, there are no reports to identify or characterize specific K+transporters inS. mutans. We identified the most important system for K+homeostasis and its role in the biofilm formation, stress tolerance, and growth. We also show the requirement of environmental K+for the activity of biofilm-forming enzymes, which explains why such high levels of K+would favor biofilm formation.

Technical services and user service improvement

2006 ◽  
Vol 27 (6/7) ◽  
pp. 505-514 ◽  
Author(s):  
Jie Huang ◽  
Katherine Wong
Keyword(s):  
Point Of View ◽  
Service Improvement ◽  
Key Factors ◽  
Content Type ◽  
University Of Oklahoma ◽  
Online Catalog ◽  
Efficient Processing ◽  
The University ◽  
Technical Services

PurposeFrom the cataloging librarians' point of view, this paper aims to present how technical services, especially the cataloging department, can play important roles in the improvement of user services.Design/methodology/approachThe paper examines the practices of the University of Oklahoma Libraries.FindingsThe paper identifies several aspects in which technical services can enhance the quality of user services, especially in the cataloging department. A library's online catalog becomes the first point of access to the library's information resources. Its quality can be improved and enriched in many ways to raise users’ satisfaction. Aside from the improvement in technical aspects, efforts should also be made to promote collaboration between technical and public services so as to ensure efficient processing of materials and to meet the needs of library users.Originality/valueThe value of the paper is in showing that the quality of an online catalog and the cooperation between public and technical services are two of the key factors in achieving high quality of user services.

Qualitative generalising in accounting research: concepts and strategies

2016 ◽  
Vol 29 (6) ◽  
pp. 1100-1131 ◽  
Author(s):  
Lee D. Parker ◽  
Deryl Northcott
Keyword(s):  
Design Methodology ◽  
Research Literature ◽  
Key Factors ◽  
General Applicability ◽  
Information Systems Management ◽  
Content Type ◽  
Accounting Research ◽  
Research Findings ◽  
Quality Of Research

Purpose – The purpose of this paper is to identify and articulate concepts and approaches to qualitative generalisation that will offer qualitative accounting researchers avenues for enhancing and justifying the general applicability of their research findings and conclusions. Design/methodology/approach – The study and arguments draw from multidisciplinary approaches to this issue. The analysis and theorising is based on published qualitative research literatures from the fields of education, health sciences, sociology, information systems, management and marketing, as well as accounting. Findings – The paper develops two overarching generalisation concepts for application by qualitative accounting researchers. These are built upon a number of qualitative generalisation concepts that have emerged in the multidisciplinary literatures. It also articulates strategies for enhancing the generalisability of qualitative accounting research findings. Research limitations/implications – The paper provides qualitative accounting researchers with understandings, arguments and justifications for the generalisability of their research and the related potential for wider accounting and societal contributions. It also articulates the key factors that impact on the quality of research generalisation that qualitative researchers can offer. Originality/value – This paper presents the most comprehensively sourced and developed approach to the concepts, strategies and unique deliverables of qualitative generalising hitherto available in the accounting research literature.

Opportunity zones: Do tax benefits go to the most distressed communities?

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
James R. Barth ◽  
Yanfei Sun ◽  
Shen Zhang
Keyword(s):  
African American ◽  
Family Income ◽  
Tax Incentives ◽  
Poverty Rate ◽  
Key Factors ◽  
Median Family Income ◽  
Content Type ◽  
Explanatory Factors ◽  
Tax Benefits ◽  
Selection Of

Purpose The exact criteria used by state governors for choosing opportunity zones (OZs) are not publicly available. This paper aims to examine whether state governors selected the most distressed communities, or those with the highest proportions of minorities, as OZs. Design/methodology/approach This paper compares the distressed communities chosen as OZs in states throughout the country to an equal number of those eligible distressed communities but not selected. Moreover, this paper uses regression analysis to determine whether the poverty rate, median family income, population, percentage of population that is minority and the percentage of population that is African American are significant explanatory factors in the choice of OZs. Findings After describing the tax incentives for investing in OZs, this paper documents that governors did not select many of the most distressed communities, or those with high proportions of minorities, in their individual states. Originality/value This paper describes in some detail the way in which investors may generate tax benefits by investing in eligible property or businesses in OZs. It also examines the extent to which the degree of poverty and the percentage of the population that is minority (and African American) were key factors in the selection of OZs. It arises an issue that the chosen communities are not necessarily those most in need of more investment or those heavily populated by minorities, particularly African Americans.

scholarly journals Downregulation of the Central Noradrenergic System by Toxoplasma gondii Infection

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Isra Alsaady ◽  
Ellen Tedford ◽  
Mohammad Alsaad ◽  
Greg Bristow ◽  
Shivali Kohli ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Infection Intensity ◽  
Noradrenergic System ◽  
Neural Cells ◽  
Mrna Levels ◽  
Female Rat ◽  
Motor Impairments ◽  
Content Type ◽  
General Response

ABSTRACT Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. In the study described here, the noradrenergic system was found to be suppressed with decreased levels of norepinephrine (NE) in brains of infected animals and in infected human and rat neural cells in vitro. The mechanism responsible for the NE suppression was found to be downregulation of dopamine β-hydroxylase (DBH) gene expression, encoding the enzyme that synthesizes norepinephrine from dopamine, with downregulation observed in vitro and in infected brain tissue, particularly in the dorsal locus coeruleus/pons region. The downregulation was sex specific, with males expressing reduced DBH mRNA levels whereas females were unchanged. Rather, DBH expression correlated with estrogen receptor in the female rat brains for this estrogen-regulated gene. DBH silencing was not a general response of neurons to infection, as human cytomegalovirus did not downregulate DBH expression. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically infected animals, with a high correlation between DBH expression and infection intensity. A decrease in DBH expression in noradrenergic neurons can elevate dopamine levels, which provides a possible explanation for mixed observations of changes in this neurotransmitter with infection. Decreased NE is consistent with the loss of coordination and motor impairments associated with toxoplasmosis. Further, the altered norepinephrine synthesis observed here may, in part, explain behavioral effects of infection and associations with mental illness.

scholarly journals Comprehensive Characterization of Toxoplasma Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Yong Fu ◽  
Xia Cui ◽  
Sai Fan ◽  
Jing Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Toxoplasma Gondii ◽  
Binding Protein ◽  
Ankyrin Repeat ◽  
Type I ◽  
Type Ii ◽  
Content Type ◽  
High K ◽  
Acyl Coenzyme A

ABSTRACT Acyl coenzyme A (CoA)-binding protein (ACBP) can bind acyl-CoAs with high specificity and affinity, thus playing multiple roles in cellular functions. Mitochondria of the apicomplexan parasite Toxoplasma gondii have emerged as key organelles for lipid metabolism and signaling transduction. However, the rationale for how this parasite utilizes acyl-CoA-binding protein to regulate mitochondrial lipid metabolism remains unclear. Here, we show that an ankyrin repeat-containing protein, TgACBP2, is localized to mitochondria and displays active acyl-CoA-binding activities. Dephosphorylation of TgACBP2 is associated with relocation from the plasma membrane to the mitochondria under conditions of regulation of environmental [K+]. Under high [K+] conditions, loss of ACBP2 induced mitochondrial dysfunction and apoptosis-like cell death. Disruption of ACBP2 caused growth and virulence defects in the type II strain but not in type I parasites. Interestingly, mitochondrial association factor-1 (MAF1)-mediated host mitochondrial association (HMA) restored the growth ability of ACBP2-deficient type II parasites. Lipidomics analysis indicated that ACBP2 plays key roles in the cardiolipin metabolism of type II parasites and that MAF1 expression complemented the lipid metabolism defects of ACBP2-deficient type II parasites. In addition, disruption of ACBP2 caused attenuated virulence of Prugniuad (Pru) parasites for mice. Taking the results collectively, these data indicate that ACBP2 is critical for the growth and virulence of type II parasites and for the growth of type I parasites under high [K+] conditions. IMPORTANCE Toxoplasma gondii is one of the most successful human parasites, infecting nearly one-third of the total world population. T. gondii tachyzoites residing within parasitophorous vacuoles (PVs) can acquire fatty acids both via salvage from host cells and via de novo synthesis pathways for membrane biogenesis. However, although fatty acid fluxes are known to exist in this parasite, how fatty acids flow through Toxoplasma lipid metabolic organelles, especially mitochondria, remains unknown. In this study, we demonstrated that Toxoplasma expresses an active ankyrin repeat containing protein TgACBP2 to coordinate cardiolipin metabolism. Specifically, HMA acquisition resulting from heterologous functional expression of MAF1 rescued growth and lipid metabolism defects in ACBP2-deficient type II parasites, manifesting the complementary role of host mitochondria in parasite cardiolipin metabolism. This work highlights the importance of TgACBP2 in parasite cardiolipin metabolism and provides evidence for metabolic association of host mitochondria with T. gondii.

The combination of different open innovations: a longitudinal case study

2019 ◽  
Vol 13 (2) ◽  
pp. 342-362
Author(s):  
Xiaodong Yuan ◽  
Xiaotao Li
Keyword(s):  
New Product Development ◽  
Open Innovation ◽  
Point Of View ◽  
Longitudinal Case Study ◽  
Key Factors ◽  
Content Type ◽  
Strategic Direction ◽  
Different Types ◽  
Innovation Capacity

Purpose The purpose of this paper is to explore how an organization can combine different types of open innovations and what are the key factors that may influence the combination of different open innovations. Design/methodology/approach The basic methodology of this paper is the longitudinal inductive analysis within the conceptual framework of the open innovation proposed by Dahlander and Gann (2010). In this case study of Xiaomi Tech Inc., the open innovation combination is investigated through examining 25 new products created between August 2010 and December 2016 in terms of four general types: acquiring, sourcing, selling and revealing open innovation. Findings In practice, the combination of different types of open innovations can be realized. A firm may combine different open innovations at three levels: a single product level, a related product cluster level and a company level. In addition, different open innovations can be combined in diverse modes. The purpose of combining different types of open innovations is to overcome the disadvantages of each type and to exploit the advantages of all different types. Many factors may affect a firm’s option of how to combine open innovations. At different development stages, a firm may make and implement corresponding strategic direction based on its innovation capacity and internal resource. For a given strategy, the firm needs to create profits and manage intellectual property in the implementation of open innovations. These factors are interacted each other, rather than isolated. Originality/value The findings of this paper are helpful for better understanding how and why an organization can combine different types of open innovations. From a managerial point of view, an organization may combine different types of open innovations to leverage advantages and avoid disadvantages of each certain type of open innovation. An appropriate combination of different open innovations can effectively improve new product development.

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