Dictyostelium discoideum—a model for many reasons

Abstract

The social amoeba or cellular slime mould Dictyostelium discoideum is a "professional" phagocyte that has long been recognized for its value as a biomedical model organism, particularly in studying the actomyosin cytoskeleton and chemotactic motility in non-muscle cells. The complete genome sequence of D. discoideum is known, it is genetically tractable, readily grown clonally as a eukaryotic microorganism and is highly accessible for biochemical, cell biological and physiological studies. These are the properties it shares with other microbial model organisms. However, Dictyostelium combines these with a unique life style, with motile unicellular and multicellular stages, and multiple cell types that offer for study an unparalleled variety of phenotypes and associated signalling pathways. These advantages have led to its recent emergence as a valuable model organism for studying the molecular pathogenesis and treatment of human disease, including a variety of infectious diseases caused by bacterial and fungal pathogens. Perhaps surprisingly, this organism, without neurons or brain, has begun to yield novel insights into the cytopathology of mitochondrial diseases as well as other genetic and idiopathic disorders affecting the central nervous system. Dictyostelium has also contributed significantly to our understanding of NDP kinase, as it was the Dictyostelium enzyme whose structure was first determined and related to enzymatic activity. The phenotypic richness and tractability of Dictyostelium should provide a fertile arena for future exploration of NDPK's cellular roles.

Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

“…Under starvation, the singlecelled amoeba expresses a chemotactic signaling system to aggregate into a multicellular structure, mediated by the chemoattractant cAMP. The corresponding receptor signaling pathway and the downstream cytoskeletal machinery show remarkable similarities to motile cells of higher organisms, in particular neutrophils (2), making Dictyostelium one of the most popular models for eukaryotic cell motility and chemotaxis (3,4).…”

Nucleoside diphosphate kinases (NDPKs) in animal development

“…Slugs use the front of their rounded transparent cell bodies to focus light, and this primitive 'lens' refracts light towards the back of the slug body as a means to navigate from dark soil to the light at the soil surface. At the soil surface, the aggregate slug can differentiate into a multicellular stalk and head structure that will make spores at its distal tip, to be carried in the wind to complete its life cycle [90]. Importantly, vectorial motion to light was not the only perturbed function during induced starvation.…”

An Evolutionary Biology Approach to Understanding Neurological Disorders

“…The reason why model organisms are able to contribute so effectively to our understanding of human diseases lies in the high degree of molecular conservation found between metazoan species, and in the conserved nature of protein-protein, and other, networks (Gandhi et al, 2006). Indeed, even bacteria, plants, protists, and fungi are being exploited to explore differing aspects of biology relevant to human disease (Annesley & Fisher, 2009;Ilievska et al, 2011;McGary et al, 2010;Spradling et al, 2006). …”

“…Not only do many of the genes encoding ESCRT subunits appear to have caretaker functions, with mutations being linked to both cancer and neurological disorders, these genes also have an origin pre-dating the metazoan lineage (reviewed by Ilievska et al, 2011). Model organisms, such as the amoeba, Dictyostelium discoideum (Annesley & Fisher, 2009;Williams RS et al, 2006), can therefore be used to study the fundamental molecular roles of these proteins (Blanc et al, 2009;Mattei et al, 2006). Overall, the evolutionary age of cancer genes parallels their role in human cancer etiology (Fig.…”