Local and systemic effects of targeted zinc redistribution in Drosophila neuronal and gastrointestinal tissues

Richards, Christopher D.; Burke, Richard

doi:10.1007/s10534-015-9881-5

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…Exit of zinc from the ECs into the circulation appears to be primarily mediated by zinc exporters ZnT63C and ZnT77C ( Wang et al 2009 ; Qin et al 2013 ), and may not require handling by intracellular organelles ( Qin et al 2013 ; Richards and Burke 2015 ). ZnT63C is expressed at the basal membrane of a subset of ECs in an unspecified midgut region, as well as in Malpighian tubules.…”

Section: Functionsmentioning

confidence: 99%

Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster

2018

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The gastrointestinal tract has recently come to the forefront of multiple research fields. It is now recognized as a major source of signals modulating food intake, insulin secretion and energy balance. It is also a key player in immunity and, through its interaction with microbiota, can shape our physiology and behavior in complex and sometimes unexpected ways. The insect intestine had remained, by comparison, relatively unexplored until the identification of adult somatic stem cells in the Drosophila intestine over a decade ago. Since then, a growing scientific community has exploited the genetic amenability of this insect organ in powerful and creative ways. By doing so, we have shed light on a broad range of biological questions revolving around stem cells and their niches, interorgan signaling and immunity. Despite their relatively recent discovery, some of the mechanisms active in the intestine of flies have already been shown to be more widely applicable to other gastrointestinal systems, and may therefore become relevant in the context of human pathologies such as gastrointestinal cancers, aging, or obesity. This review summarizes our current knowledge of both the formation and function of the Drosophila melanogaster digestive tract, with a major focus on its main digestive/absorptive portion: the strikingly adaptable adult midgut.

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Section: Functionsmentioning

confidence: 99%

Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster

2018

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“…In Drosophila , dZip42C .1, dZip42C .2 and dZip89B (likely orthologues of hZIP1 , hZIP2 and hZIP3 ) are the most important transporters for absorption of Zn from the intestinal lumen. All of them are located in the apical membrane of enterocytes ( Figure 1 C), and their expression can be affected by dietary Zn levels ( dZip42C.1 and dZip42C .2) [ 119 ] or can be independent of Zn content acting as a constitutive Zn transporter with a lower affinity for this metal ( dZip89B ) [ 120 ].…”

Section: Drosophila Genes Involved In Metal Hommentioning

confidence: 99%

Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity

Calap-Quintana

González-Fernández

Sebastiá-Ortega

et al. 2017

IJMS

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Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided.

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“…Therefore, it is instrumental in the excretion of Zn from the organism and accordingly, silencing of dZip71B triggers Zn accumulation in the body and these flies are more sensitive to Zn overload (Yin et al, 2017 ). When overexpressed, dZip71B acts as a very efficient and potent Zn transporter able to create a toxic Zn accumulation on its own (Richards and Burke, 2015 ). Interestingly, both reports highlight cell-specific regulation of Zn metabolism.…”

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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Local and systemic effects of targeted zinc redistribution in Drosophila neuronal and gastrointestinal tissues

Cited by 11 publications

References 24 publications

Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster

Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster

Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity

Copper and Zinc Homeostasis: Lessons from Drosophila melanogaster

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