Natural and laboratory mutations in kuzbanian are associated with zinc stress phenotypes in Drosophila melanogaster

Manh, Hung Le; Guio, Lain; Merenciano, Miriam; Rovira, Quirze; González, Josefa

doi:10.1038/srep42663

Cited by 9 publications

(7 citation statements)

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“…The defect in this new level of control of Zn homeostasis was probably due to a failure in the endosomal recycling of proteins back to the membrane that hence reduced the uptake of Zn (Wang et al, 2014 ). Very recently, kuzbanian ( kuz ) a gene that was already described as a target of dMTF-1 (Yepiskoposyan et al, 2006 ) has been found to confer tolerance to Zn when overexpressed (Le Manh et al, 2017 ).…”

Section: Regulation Of Zn Metabolism In Drosophilamentioning

confidence: 99%

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Navarro

Schneuwly

2017

Front. Genet.

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Maintenance of metal homeostasis is crucial for many different enzymatic activities and in turn for cell function and survival. In addition, cells display detoxification and protective mechanisms against toxic accumulation of metals. Perturbation of any of these processes normally leads to cellular dysfunction and finally to cell death. In the last years, loss of metal regulation has been described as a common pathological feature in many human neurodegenerative diseases. However, in most cases, it is still a matter of debate whether such dyshomeostasis is a primary or a secondary downstream defect. In this review, we will summarize and critically evaluate the contribution of Drosophila to model human diseases that involve altered metabolism of metals or in which metal dyshomeostasis influence their pathobiology. As a prerequisite to use Drosophila as a model, we will recapitulate and describe the main features of core genes involved in copper and zinc metabolism that are conserved between mammals and flies. Drosophila presents some unique strengths to be at the forefront of neurobiological studies. The number of genetic tools, the possibility to easily test genetic interactions in vivo and the feasibility to perform unbiased genetic and pharmacological screens are some of the most prominent advantages of the fruitfly. In this work, we will pay special attention to the most important results reported in fly models to unveil the role of copper and zinc in cellular degeneration and their influence in the development and progression of human neurodegenerative pathologies such as Parkinson's disease, Alzheimer's disease, Huntington's disease, Friedreich's Ataxia or Menkes, and Wilson's diseases. Finally, we show how these studies performed in the fly have allowed to give further insight into the influence of copper and zinc in the molecular and cellular causes and consequences underlying these diseases as well as the discovery of new therapeutic strategies, which had not yet been described in other model systems.

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Section: Regulation Of Zn Metabolism In Drosophilamentioning

confidence: 99%

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Navarro

Schneuwly

2017

Front. Genet.

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“…TE insertions are often associated with changes in gene expression under stressful conditions (Horváth et al 2017), and in D. melanogaster, several specific insertions have been linked to stress response including zinc stress (e.g. Schmidt and Robin 2011a;Guio et al 2014;Mateo et al 2014;Merenciano et al 2016;Le Manh et al 2017;Ullastres et al 2019). However, until recently only the subset of TEs annotated in the reference genome could be analyzed limiting the power of genomewide analysis for this type of structural variants.…”

Section: Transposable Element Insertions May Influence Copper Tolerancementioning

confidence: 99%

“…[64]), and in D. melanogaster, several specific insertions have been linked to stress response including zinc stress (e.g. [27][28][29][30][31][32]). However, until recently only the subset of TEs annotated in the reference genome could be analyzed, thus limiting the power of genome-wide analysis to investigate this type of structural variant.…”

Section: Transposable Element Insertions May Influence Copper Tolerancementioning

confidence: 99%

“…Schmidt andRobin 2011a;Guio et al 2014;Mateo et al 2014;Merenciano et al 2016;Ullastres et al 2019). Indeed, a natural transposable element insertion in the MTF-1 targeted gene kuzbanian has been associated with increased tolerance to zinc in adult flies, although the effect of the insertion was background dependent (Le Manh et al 2017).…”

Section: Introductionmentioning

confidence: 99%

“…[26][27][28][29][30][31]). Indeed, a natural transposable element insertion in the MTF-1 targeted gene kuzbanian has been associated with increased tolerance to zinc in adult flies, although the effect of the insertion was background dependent [32].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The genomic basis of copper tolerance inDrosophilais shaped by a complex interplay of regulatory and environmental factors

Green

Radío

Rech

et al. 2021

Preprint

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Increases in industrialisation and anthropogenic activity have resulted in an increase in pollutants released into the environment. Of these pollutants, heavy metals such as copper are particularly concerning due to their bio-accumulative nature. Due to its highly heterogeneous distribution and its dual nature as both an essential micronutrient and toxic element, the genetic basis of copper tolerance is likely shaped by a complex interplay of physiological and environmental factors. Drosophila melanogaster, a long-standing sentinel of environmental toxins, is uniquely suited for the study of copper tolerance in arthropods and other more diverse species. In this study, we utilized the natural variation present in multiple populations of D. melanogaster collected across Europe to screen for variation in copper tolerance, which we found to be highly variable both within and between locations. While these collection locations covered a wide range of atmospheric and soil pollution levels, the degree of urbanization at the collection sites, rather than any other combination of environmental factors, was linked to copper tolerance. Moreover, differential expression analysis revealed that metabolism, reproduction, and protease induction contribute to copper response in tolerant and sensitive lines to different degrees. Additionally, the greatest transcriptomic and physiological responses to copper toxicity were seen in the midgut; where preservation of gut acidity is strongly linked to greater tolerance. Overall, our study provides a unique perspective on the genetic and environmental factors that shape copper tolerance in natural D. melanogaster populations and identifies new genes and physiological traits involved in this complex phenotype.

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New Insights on the Evolution of Genome Content: Population Dynamics of Transposable Elements in Flies and Humans

Guio

González

2019

Methods in Molecular Biology

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Understanding the abundance, diversity, and distribution of TEs in genomes is crucial to understand genome structure, function, and evolution. Advances in whole-genome sequencing techniques, as well as in bioinformatics tools, have increased our ability to detect and analyze the transposable element content in genomes. In addition to reference genomes, we now have access to population datasets in which multiple individuals within a species are sequenced. In this chapter, we highlight the recent advances in the study of TE population dynamics focusing on fruit flies and humans, which represent two extremes in terms of TE abundance, diversity, and activity. We review the most recent methodological approaches applied to the study of TE dynamics as well as the new knowledge on host factors involved in the regulation of TE activity. In addition to transposition rates, we also focus on TE deletion rates and on the selective forces that affect the dynamics of TEs in genomes.

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Natural and laboratory mutations in kuzbanian are associated with zinc stress phenotypes in Drosophila melanogaster

Cited by 9 publications

References 51 publications

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

The genomic basis of copper tolerance inDrosophilais shaped by a complex interplay of regulatory and environmental factors

New Insights on the Evolution of Genome Content: Population Dynamics of Transposable Elements in Flies and Humans

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