Dictyostelium, a microbial model for brain disease

Annesley, Sarah J.; Chen, S.; Francione, Lisa M.; Sanislav, Oana; Chavan, André; Farah, Chuck S.; Piazza, Shawn W. De; Storey, Claire; Ilievska, Jasmina; Fernando, Sanjanie; Smith, Paige K.; Lay, Sui T.; Fisher, Paul R.

doi:10.1016/j.bbagen.2013.10.019

Cited by 29 publications

(35 citation statements)

References 224 publications

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“…Because of the evolutionary conservation of the huntingtin gene, lower eukaryotic systems provide the potential for understanding huntingtin function. Consequently, the model developmental organism D. discoideum (Williams et al, 2006; Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/developmentalbiology Myre, 2012;Müller-Taubenberger et al, 2013;Muñoz-Braceras et al, 2013;Annesley et al, 2014), which undergoes cellular locomotion and chemotaxis in a manner similar to human cells (Cai and Devreotes, 2011;Wang et al, 2011a;Jin, 2013), has been used to explore the role of huntingtin at the cellular level. Wang et al (2011b) and Myre et al (2011) independently disrupted htt, the ortholog of human HTT, in D. discoideum.…”

Section: Introductionmentioning

confidence: 99%

Huntingtin regulates Ca2+ chemotaxis and K+-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H+ exchanger Nhe1, in a model developmental system: Insights into its possible role in Huntington׳s disease

Wessels

Lusche

Scherer

et al. 2014

Developmental Biology

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Huntington׳s disease is a neurodegenerative disorder, attributable to an expanded trinucleotide repeat in the coding region of the human HTT gene, which encodes the protein huntingtin. These mutations lead to huntingtin fragment inclusions in the striatum of the brain. However, the exact function of normal huntingtin and the defect causing the disease remain obscure. Because there are indications that huntingtin plays a role in Ca(2+) homeostasis, we studied the deletion mutant of the HTT ortholog in the model developmental system Dictyostelium discoideum, in which Ca(2+) plays a role in receptor-regulated behavior related to the aggregation process that leads to multicellular morphogenesis. The D. discoideum htt(-)-mutant failed to undergo both K(+)-facilitated chemotaxis in spatial gradients of the major chemoattractant cAMP, and chemotaxis up a spatial gradient of Ca(2+), but behaved normally in Ca(2+)-facilitated cAMP chemotaxis and Ca(2+)-dependent flow-directed motility. This was the same phenotypic profile of the null mutant of Nhel, a monovalent cation/H(+)exchanger. The htt(-)-mutant also failed to orient correctly during natural aggregation, as was the case for the Nhel mutant. Moreover, in a K(+)-based buffer the normal localization of actin was similarly defective in both htt(-) and nhe1(-) cells in a K(+)-based buffer, and the normal localization of Nhe1 was disrupted in the htt(-) mutant. These observations demonstrate that Htt and Nhel play roles in the same specific cation-facilitated behaviors and that Nhel localization is directly or indirectly regulated by Htt. Similar cation-dependent behaviors and a similar relationship between Htt and Nhe1 have not been reported for mammalian neurons and deserves investigation, especially as it may relate to Huntington׳s disease.

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Section: Introductionmentioning

confidence: 99%

Huntingtin regulates Ca2+ chemotaxis and K+-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H+ exchanger Nhe1, in a model developmental system: Insights into its possible role in Huntington׳s disease

Wessels

Lusche

Scherer

et al. 2014

Developmental Biology

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“…The finding that mitochondrial respiratory deficiencies induce in Dictyostelium a consistent pattern of altered phenotypes has been further exploited to investigate genes involved in mitochondrial diseases (Annesley et al, 2014). It has been shown that mutations in the Dictyostelium homologues of two Parkinson's disease associated proteins, DJ-1 and HTRA2, have differential effects on mitochondrial dysfunction Chen et al, 2017).…”

Section: Dictyostelium As a Model For Biomedical Research: Recent Conmentioning

confidence: 99%

The past, present and future of Dictyostelium as a model system

Bozzaro¹

2019

Int. J. Dev. Biol.

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The social amoeba Dictyostelium discoideum has been a preferred model organism during the last 50 years, particularly for the study of cell motility and chemotaxis, phagocytosis and macropinocytosis, intercellular adhesion, pattern formation, caspase-independent cell death and more recently autophagy and social evolution. Being a soil amoeba and professional phagocyte, thus exposed to a variety of potential pathogens, D. discoideum has also proven to be a powerful genetic and cellular model for investigating host-pathogen interactions and microbial infections. The finding that the Dictyostelium genome harbours several homologs of human genes responsible for a variety of diseases has stimulated their analysis, providing new insights into the mechanism of action of the encoded proteins and in some cases into the defect underlying the disease. Recent technological developments have covered the genetic gap between mammals and non-mammalian model organisms, challenging the modelling role of the latter. Is there a future for Dictyostelium discoideum as a model organism? Peculiarities and advantages of Dictyostelium discoideum as model organismAmong the non-mammalian model organisms, Dictyostelium discoideum (in the following Dictyostelium) is unique, due to cell division and development being totally uncoupled, and because of the transition from a unicellular to a multicellular stage during the life cycle. Growing cells proliferate by binary fission but do not differentiate, whereas starving cells undergo multicellular development and differentiation without dividing and without any need for external nutrients. Thus growth and development can be studied separately, and several non-lethal mutants can be isolated

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“…For example, Dictyostelium can be used to study fundamental cellular processes without the complexity observed in other organisms. Since many human diseases share common cellular features such as mitochondrial dysfunction, aberrant lysosomal function, elevated protein aggregation, and autophagic vacuoles, studies in Dictyostelium allow for the examination of potential causative mechanisms between cellular dysfunction and pathogenesis in an organism with measurable phenotypic outcomes (Annesley et al., ). Given the metazoan‐like behavior of Dictyostelium cells, findings from this organism are highly likely to be translatable to more complex eukaryotic systems.…”

Section: Overview and Principlesmentioning

confidence: 99%

“…While a thorough discussion of this topic is beyond the scope of this review, we will briefly highlight how research in Dictyostelium has provided fresh new insight into the pathogenic mechanisms underlying Alzheimer's disease, Huntington's disease, prion diseases, and NCL. The reader is encouraged to refer to recent reviews that describe these and other forms of neurological disease that have been studied using Dictyostelium (Annesley et al., ; Cunliffe et al., ; Gilsbach & Kortholt, ; Huber, ; Malinovska & Alberti, ; Meyer et al., ; Myre, ).…”

Section: New Ways Dictyostelium Is Used Todaymentioning

confidence: 99%

Dictyostelium discoideum: A Model System for Cell and Developmental Biology

Mathavarajah

Flores

Huber

2017

CP Essential Lab Tech

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The social amoeba Dictyostelium discoideum has long served as a model system for studying fundamental processes in cell and developmental biology. This eukaryotic microbe is also recognized as a model organism for biomedical and human disease research since the genome encodes homologs of genes linked to human disease, such as those linked to cancer and neurodegeneration. Dictyostelium has a unique life cycle composed of a unicellular growth phase and a multicellular developmental phase that is induced by starvation. During its life cycle, Dictyostelium undergoes conserved cellular processes including, but not limited to, cell proliferation, phagocytosis, intercellular signaling, cell adhesion and motility, chemotaxis, and cell differentiation. The history of the organism, the resources available to researchers in the community, and the diverse ways that Dictyostelium is used in the contemporary research lab are discussed. © 2017 by John Wiley & Sons, Inc.

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Dictyostelium, a microbial model for brain disease

Cited by 29 publications

References 224 publications

Huntingtin regulates Ca2+ chemotaxis and K+-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H+ exchanger Nhe1, in a model developmental system: Insights into its possible role in Huntington׳s disease

Huntingtin regulates Ca2+ chemotaxis and K+-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H+ exchanger Nhe1, in a model developmental system: Insights into its possible role in Huntington׳s disease

The past, present and future of Dictyostelium as a model system

Dictyostelium discoideum: A Model System for Cell and Developmental Biology

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