Unfolding the Endoplasmic Reticulum of a Social Amoeba: Dictyostelium discoideum as a New Model for the Study of Endoplasmic Reticulum Stress

Abstract

The endoplasmic reticulum (ER) is a membranous network with an intricate dynamic architecture necessary for various essential cellular processes. Nearly one third of the proteins trafficking through the secretory pathway are folded and matured in the ER. Additionally, it acts as calcium storage, and it is a main source for lipid biosynthesis. The ER is highly connected with other organelles through regions of membrane apposition that allow organelle remodeling, as well as lipid and calcium traffic. Cells are under constant changes due to metabolic requirements and environmental conditions that challenge the ER network’s maintenance. The unfolded protein response (UPR) is a signaling pathway that restores homeostasis of this intracellular compartment upon ER stress conditions by reducing the load of proteins, and by increasing the processes of protein folding and degradation. Significant progress on the study of the mechanisms that restore ER homeostasis was achieved using model organisms such as yeast, Arabidopsis, and mammalian cells. In this review, we address the current knowledge on ER architecture and ER stress response in Dictyostelium discoideum. This social amoeba alternates between unicellular and multicellular phases and is recognized as a valuable biomedical model organism and an alternative to yeast, particularly for the presence of traits conserved in animal cells that were lost in fungi.

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

“…Interestingly, these are the only ER-resident proteins among the family of NCL proteins. Current knowledge indicates that the Dictyostelium ER shares several functions with the ER in mammalian cells including calcium storage, lipid biosynthesis, and the unfolded protein response [40]. Furthermore, Dictyostelium is the only microorganism known to encode homologs of human calnexin and calreticulin [41].…”

Tunicamycin Sensitivity-Suppression by High Gene Dosage Reveals New Functions of the Yeast Hog1 MAP Kinase

“…All organisms are exposed to adverse conditions that decrease the capacity of the ER to fulfill these processes, leading to the production and accumulation of misfolded proteins, inducing a condition known as endoplasmic reticulum stress (ER stress). ER stress triggers a cellular response that includes the unfolded protein response (UPR), which is a conserved signaling pathway present in all eukaryotic cells, including yeast [1], Dictyostelium discoideum [2], plants [3], and mammals [4]. In the yeast Saccharomyces cerevisiae the UPR consists of an endoplasmic reticulum membrane sensor named Ire1 [5], which in the presence of misfolded proteins oligomerises and autophosphorylates [6,7]; this in turn triggers its cytoplasmic endonuclease activity, which processes the HAC1 pre-mRNA [8].…”

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

“…The cellular slime molds are a group of soil microorganisms that belong to the eukaryotic kingdom Amoebozoa, which, according to recent taxonomic research, is distinct from the fungus kingdom Mycota (Figure 1) [5,6,7]. For about 80 years, the cellular slime mold Dictyostelium discoideum has been used as a model organism for the study of eukaryotic cell functions (e.g., division, differentiation, chemotaxis, autophagy and death) [8,9,10,11,12,13,14,15,16,17,18,19] mainly because of its simple life cycle and ease of handling. Recently, D. discoideum has also been used as a model organism for the study of human diseases and estimation of drug effects [17,20,21,22,23,24].…”