scholarly journals Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Robert J. Huber
Keyword(s):  
Dictyostelium Discoideum ◽  
Mammalian Cells ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Common Disease ◽  
Cellular Mechanisms ◽  
Molecular Networking ◽  
Social Amoeba ◽  
Cellular Models ◽  
The Social

Abstract The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.

scholarly journals Recent Insights into NCL Protein Function Using the Model Organism Dictyostelium discoideum

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 115 ◽  
Author(s):  
Meagan McLaren ◽  
Sabateeshan Mathavarajah ◽  
Robert Huber
Keyword(s):  
Dictyostelium Discoideum ◽  
Neurological Disorders ◽  
Protein Function ◽  
Model Organism ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Biomedical Model ◽  
The Social ◽  
Wide Range ◽  
Poor Understanding

The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating neurological disorders that have a global distribution and affect people of all ages. Commonly known as Batten disease, this form of neurodegeneration is linked to mutations in 13 genetically distinct genes. The precise mechanisms underlying the disease are unknown, in large part due to our poor understanding of the functions of NCL proteins. The social amoeba Dictyostelium discoideum has proven to be an exceptional model organism for studying a wide range of neurological disorders, including the NCLs. The Dictyostelium genome contains homologs of 11 of the 13 NCL genes. Its life cycle, comprised of both single-cell and multicellular phases, provides an excellent system for studying the effects of NCL gene deficiency on conserved cellular and developmental processes. In this review, we highlight recent advances in NCL research using Dictyostelium as a biomedical model.

scholarly journals Amino Acid Repeats Cause Extraordinary Coding Sequence Variation in the Social Amoeba Dictyostelium discoideum

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e46150 ◽  
Author(s):  
Clea Scala ◽  
Xiangjun Tian ◽  
Natasha J. Mehdiabadi ◽  
Margaret H. Smith ◽  
Gerda Saxer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Dictyostelium Discoideum ◽  
Sequence Variation ◽  
Social Amoeba ◽  
Coding Sequence ◽  
Amino Acid Repeats ◽  
The Social

scholarly journals Microbe Profile: Dictyostelium discoideum: model system for development, chemotaxis and biomedical research

Microbiology ◽  
2021 ◽  
Author(s):  
Catherine J. Pears ◽  
Julian D. Gross
Keyword(s):  
Pattern Formation ◽  
Cell Motility ◽  
Dictyostelium Discoideum ◽  
Biomedical Research ◽  
Model System ◽  
Developmental Pattern ◽  
Social Amoeba ◽  
The Social ◽  
Host Pathogen ◽  
Soil Amoeba

The social amoeba Dictyostelium discoideum is a versatile organism that is unusual in alternating between single-celled and multi-celled forms. It possesses highly-developed systems for cell motility and chemotaxis, phagocytosis, and developmental pattern formation. As a soil amoeba growing on microorganisms, it is exposed to many potential pathogens; it thus provides fruitful ways of investigating host-pathogen interactions and is emerging as an influential model for biomedical research.

scholarly journals Role of epigenetics in unicellular to multicellular transition in Dictyostelium

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Simon Yuan Wang ◽  
Elizabeth Ann Pollina ◽  
I-Hao Wang ◽  
Lindsay Kristina Pino ◽  
Henry L. Bushnell ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Orthologous Gene ◽  
Chromatin Accessibility ◽  
Critical Event ◽  
H3k4 Methylation ◽  
Social Amoeba ◽  
The Social ◽  
Conserved Genes ◽  
Multicellular Organisms

Abstract Background The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth between both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity. Results While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and orthologous gene analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity in Dictyostelium. Conclusions These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate multicellularity in Dictyostelium discoideum and raise exciting possibilities about the role of epigenetics in the evolution of multicellularity more broadly.

scholarly journals (Auto)Biographical reflections on the contributions of William F. Loomis (1940-2016) to Dictyostelium biology

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 343-357
Author(s):  
Adam Kuspa ◽  
Gad Shaulsky
Keyword(s):  
Cell Differentiation ◽  
Molecular Biology ◽  
Genetic Control ◽  
Dictyostelium Discoideum ◽  
University Of California ◽  
High Dimensional ◽  
Social Amoeba ◽  
The Social ◽  
The University ◽  
High Dimensional Datasets

William Farnsworth Loomis studied the social amoeba Dictyostelium discoideum for more than fifty years as a professor of biology at the University of California, San Diego, USA. This biographical reflection describes Dr. Loomis’ major scientific contributions to the field within a career arc that spanned the early days of molecular biology up to the present day where the acquisition of high-dimensional datasets drive research. Dr. Loomis explored the genetic control of social amoeba development, delineated mechanisms of cell differentiation, and significantly advanced genetic and genomic technology for the field. The details of Dr. Loomis’ multifaceted career are drawn from his published work, from an autobiographical essay that he wrote near the end of his career and from extensive conversations between him and the two authors, many of which took place on the deck of his beachfront home in Del Mar, California.

scholarly journals Methods to Monitor and Quantify Autophagy in the Social Amoeba Dictyostelium discoideum

Cells ◽  
2017 ◽  
Vol 6 (3) ◽  
pp. 18 ◽  
Author(s):  
Eunice Domínguez-Martín ◽  
Elena Cardenal-Muñoz ◽  
Jason King ◽  
Thierry Soldati ◽  
Roberto Coria ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Social Amoeba ◽  
The Social

scholarly journals Modelling of Neuronal Ceroid Lipofuscinosis Type 2 in Dictyostelium discoideum Suggests That Cytopathological Outcomes Result from Altered TOR Signalling

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 469 ◽  
Author(s):  
Paige K. Smith ◽  
Melodi G. Sen ◽  
Paul R. Fisher ◽  
Sarah J. Annesley
Keyword(s):  
Dictyostelium Discoideum ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Clinical Manifestations ◽  
Batten Disease ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Antisense Inhibition ◽  
Phenotypic Characterisation ◽  
Cellular Slime ◽  
Multiple Cell

The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative disorders with similar clinical manifestations whose precise mechanisms of disease are presently unknown. We created multiple cell lines each with different levels of reduction of expression of the gene coding for the type 2 variant of the disease, Tripeptidyl peptidase (Tpp1), in the cellular slime mould Dictyostelium discoideum. Knocking down Tpp1 in Dictyostelium resulted in the accumulation of autofluorescent material, a characteristic trait of Batten disease. Phenotypic characterisation of the mutants revealed phenotypic deficiencies in growth and development, whilst endocytic uptake of nutrients was enhanced. Furthermore, the severity of the phenotypes correlated with the expression levels of Tpp1. We propose that the phenotypic defects are due to altered Target of Rapamycin (TOR) signalling. We show that treatment of wild type Dictyostelium cells with rapamycin (a specific TOR complex inhibitor) or antisense inhibition of expression of Rheb (Ras homologue enriched in the brain) (an upstream TOR complex activator) phenocopied the Tpp1 mutants. We also show that overexpression of Rheb rescued the defects caused by antisense inhibition of Tpp1. These results suggest that the TOR signalling pathway is responsible for the cytopathological outcomes in the Dictyostelium Tpp1 model of Batten disease.

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