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Cells & Development Dec 2021Macropinocytosis is a form of endocytosis performed by ruffles and cups of the plasma membrane. These close to entrap droplets of medium into micron-sized vesicles,... (Review)
Review
Macropinocytosis is a form of endocytosis performed by ruffles and cups of the plasma membrane. These close to entrap droplets of medium into micron-sized vesicles, which are trafficked through the endocytic system, their contents digested and useful products absorbed. Macropinocytosis is constitutive in certain immune cells and stimulated in many other cells by growth factors. It occurs across the animal kingdom and in amoebae, implying a deep evolutionary history. Its scientific history goes back 100 years, but increasingly work is focused on its medical importance in the immune system, cancer cell feeding, and as a backdoor into cells for viruses and drugs. Macropinocytosis is driven by the actin cytoskeleton whose dynamics can be appreciated with lattice light sheet microscopy: this reveals a surprising variety of routes for forming macropinosomes. In Dictyostelium amoebae, macropinocytic cups are organized around domains of PIP3 and active Ras and Rac in the plasma membrane. These attract activators of the Arp2/3 complex to their periphery, creating rings of actin polymerization that shape the cups. The size of PIP3 domains is controlled by RasGAPs, such as NF1, and the lipid phosphatase, PTEN. It is likely that domain dynamics determine the shape, evolution and closing of macropinocytic structures.
Topics: Actin Cytoskeleton; Amoeba; Animals; Biology; Dictyostelium; Endocytosis; Pinocytosis
PubMed: 34175511
DOI: 10.1016/j.cdev.2021.203713 -
Journal of Biosciences 2022is a species of free-living soil amoeba that feeds on bacteria that grow on decaying vegetation. Though the present account deals with , I use the more colloquial...
is a species of free-living soil amoeba that feeds on bacteria that grow on decaying vegetation. Though the present account deals with , I use the more colloquial 'dictyostelium' in this article. In 1989, as a new PI, I began to study the response of D. discoideum amoebae to pisatin. Pisatin is the major phytoalexin of the pea plant (). Phytoalexins are antifungal compounds made by plants in response to infection and injury. No other group has studied any dictyostelium vis-a`-vis any phytoalexin. Evidence for saying so comes from PubMed: four papers show up with the keywords 'dictyostelium', and 'phytoalexin', all from my lab. Why did we 'plough this lonely furrow' and what did we uncover?
Topics: Dictyostelium; Pisum sativum; Antifungal Agents; Bacteria
PubMed: 36510437
DOI: No ID Found -
The International Journal of... 2019In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other.... (Review)
Review
In the last few decades, we have learned a considerable amount about how eukaryotic cells communicate with each other, and what it is the cells are telling each other. The simplicity of Dictyostelium discoideum, and the wide variety of available tools to study this organism, makes it the equivalent of a hydrogen atom for cell and developmental biology. Studies using Dictyostelium have pioneered a good deal of our understanding of eukaryotic cell communication. In this review, we will present a brief overview of how Dictyostelium cells use extracellular signals to attract each other, repel each other, sense their local cell density, sense whether the nearby cells are starving or stressed, count themselves to organize the formation of structures containing a regulated number of cells, sense the volume they are in, and organize their multicellular development. Although we are probably just beginning to learn what the cells are telling each other, the elucidation of Dictyostelium extracellular signals has already led to the development of possible therapeutics for human diseases.
Topics: Adenine; Adenosine Triphosphate; Ammonia; Cell Communication; Chemotactic Factors; Culture Media, Conditioned; Cyclic AMP; Dictyostelium; Morphogenesis; Polyketides; Polyphosphates
PubMed: 31840778
DOI: 10.1387/ijdb.190259rg -
Current Opinion in Structural Biology Jun 2019O-Glycosylation is an increasingly recognized modification of intracellular proteins in all kingdoms of life, and its occurrence in protists has been investigated to... (Review)
Review
O-Glycosylation is an increasingly recognized modification of intracellular proteins in all kingdoms of life, and its occurrence in protists has been investigated to understand its evolution and its roles in the virulence of unicellular pathogens. We focus here on two kinds of glycoregulation found in unicellular eukaryotes: one is a simple O-fucose modification of dozens if not hundreds of Ser/Thr-rich proteins, and the other a complex pentasaccharide devoted to a single protein associated with oxygen sensing and the assembly of polyubiquitin chains. These modifications are not required for life but contingently modulate biological processes in the social amoeba Dictyostelium and the human pathogen Toxoplasma gondii, and likely occur in diverse unicellular protists. O-Glycosylation that is co-localized in the cytoplasm allows for glycoregulation over the entire life of the protein, contrary to the secretory pathway where glycosylation usually occurs before its delivery to its site of function. Here, we interpret cellular roles of nucleocytoplasmic glycans in terms of current evidence for their effects on the conformation and dynamics of protist proteins, to serve as a guide for future studies to examine their broader significance.
Topics: Cell Nucleus; Cytoplasm; Dictyostelium; Glycoproteins; Glycosylation; Toxoplasma
PubMed: 31128470
DOI: 10.1016/j.sbi.2019.03.031 -
Cells Jan 2021The Special Issue of on "Ubiquitin and Autophagy" is a tribute to the multifaceted role of ubiquitin and autophagic ubiquitin-like (UBL) proteins in the...
The Special Issue of on "Ubiquitin and Autophagy" is a tribute to the multifaceted role of ubiquitin and autophagic ubiquitin-like (UBL) proteins in the autophagy-related (ATG) pathways [...].
Topics: Animals; Autophagy; Caenorhabditis elegans; Dictyostelium; Humans; Proteasome Endopeptidase Complex; Ubiquitin
PubMed: 33435134
DOI: 10.3390/cells10010116 -
Journal of Immunology (Baltimore, Md. :... Jul 2022A considerable amount is known about how eukaryotic cells move toward an attractant, and the mechanisms are conserved from to human neutrophils. Relatively little is...
A considerable amount is known about how eukaryotic cells move toward an attractant, and the mechanisms are conserved from to human neutrophils. Relatively little is known about chemorepulsion, where cells move away from a repellent signal. We previously identified pathways mediating chemorepulsion in , and here we show that these pathways, including Ras, Rac, protein kinase C, PTEN, and ERK1 and 2, are required for human neutrophil chemorepulsion, and, as with chemorepulsion, PI3K and phospholipase C are not necessary, suggesting that eukaryotic chemorepulsion mechanisms are conserved. Surprisingly, there were differences between male and female neutrophils. Inhibition of Rho-associated kinases or Cdc42 caused male neutrophils to be more repelled by a chemorepellent and female neutrophils to be attracted to the chemorepellent. In the presence of a chemorepellent, compared with male neutrophils, female neutrophils showed a reduced percentage of repelled neutrophils, greater persistence of movement, more adhesion, less accumulation of PI(3,4,5)P, and less polymerization of actin. Five proteins associated with chemorepulsion pathways are differentially abundant, with three of the five showing sex dimorphism in protein localization in unstimulated male and female neutrophils. Together, this indicates a fundamental difference in a motility mechanism in the innate immune system in men and women.
Topics: Actins; Chemotaxis; Dictyostelium; Female; Humans; Male; Neutrophils; Sex Characteristics
PubMed: 35793910
DOI: 10.4049/jimmunol.2101103 -
Microbiology (Reading, England) Feb 2020
Topics: Dictyostelium; Gastrointestinal Microbiome; Humans; Metabolic Networks and Pathways; Microbiology; Pseudomonas; Signal Transduction
PubMed: 32122459
DOI: 10.1099/mic.0.000901 -
Scientific Reports Dec 2021It has been experimentally reported that chemotactic cells exhibit cellular memory, that is, a tendency to maintain the migration direction despite changes in the...
It has been experimentally reported that chemotactic cells exhibit cellular memory, that is, a tendency to maintain the migration direction despite changes in the chemoattractant gradient. In this study, we analyzed a phenomenological model assuming the presence of cellular inertia, as well as a response time in motility, resulting in the reproduction of the cellular memory observed in the previous experiments. According to the analysis, the cellular motion is described by the superposition of multiple oscillative functions induced by the multiplication of the oscillative polarity and motility. The cellular intertia generates cellular memory by regulating phase differences between those oscillative functions. By applying the theory to the experimental data, the cellular inertia was estimated at [Formula: see text] min. In addition, physiological parameters, such as response time in motility and intracellular processing speed, were also evaluated. The agreement between the experiemental data and theory suggests the possibility of the presence of the response time in motility, which has never been biologically verified and should be explored in the future.
Topics: Algorithms; Animals; Cell Physiological Phenomena; Chemotaxis; Dictyostelium; Humans; Models, Biological
PubMed: 34893617
DOI: 10.1038/s41598-021-02384-y -
The International Journal of... 2019Sex in Dictyostelia involves a remarkable form of cannibalism in which zygotes attract large numbers of surrounding amoebae and then ingest them. Before they are... (Review)
Review
Sex in Dictyostelia involves a remarkable form of cannibalism in which zygotes attract large numbers of surrounding amoebae and then ingest them. Before they are consumed, the attracted amoebae help the zygote by synthesising an outer wall around the aggregate that traps them inside and helps to protect the mature developed zygotic structure, the macrocyst. Competition between cells vying to contribute genetically to zygotes and through to the next generation seems likely to have promoted the evolution of several unusual features of dictyostelid sex: individual species often have more than two mating types, increasing haploid cells' chances of matching with a compatible partner, and fusion of many gametes to form transient syncytia allows cytoplasmic mixing and lateral transmission of mitochondrial genomes. This review will summarise recent advances in our understanding of mating-type determination, gamete fusion, and inheritance in Dictyostelium, and highlight the key gaps in our understanding of this fascinating set of phenomena.
Topics: Cell Communication; Cell Nucleus; Cytoplasm; Dictyostelium; Genome; Germ Cells; Haploidy; Meiosis; Mitochondria; Reproduction
PubMed: 31840782
DOI: 10.1387/ijdb.190183gb -
The International Journal of... 2019The well-orchestrated multicellular life cycle of Dictyostelium discoideum has fascinated biologists for over a century. Self-organisation of its amoebas into... (Review)
Review
The well-orchestrated multicellular life cycle of Dictyostelium discoideum has fascinated biologists for over a century. Self-organisation of its amoebas into aggregates, migrating slugs and fruiting structures by pulsatile cAMP signalling and their ability to follow separate differentiation pathways in well-regulated proportions continue to be topics under investigation. A striking aspect of D. discoideum development is the recurrent use of cAMP as chemoattractant, differentiation inducing signal and second messenger for other signals that control the developmental programme. D. discoideum is one of >150 species of Dictyostelia and aggregative life styles similar to those of Dictyostelia evolved many times in eukaryotes. Here we review experimental studies investigating how phenotypic complexity and cAMP signalling co-evolved in Dictyostelia. In addition, we summarize comparative genomic studies of multicellular Dictyostelia and unicellular Amoebozoa aimed to identify evolutionary conservation and change in all genes known to be essential for D. discoideum development.
Topics: Biological Evolution; Cell Differentiation; Cyclic AMP; Dictyostelium; Gene Expression Regulation; Genome; Genomics; Phenotype; Phylogeny; Protein Domains; Signal Transduction
PubMed: 31840775
DOI: 10.1387/ijdb.190108ps