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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 -
Nucleic Acids Research Jan 2022The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure...
The AlphaFold Protein Structure Database (AlphaFold DB, https://alphafold.ebi.ac.uk) is an openly accessible, extensive database of high-accuracy protein-structure predictions. Powered by AlphaFold v2.0 of DeepMind, it has enabled an unprecedented expansion of the structural coverage of the known protein-sequence space. AlphaFold DB provides programmatic access to and interactive visualization of predicted atomic coordinates, per-residue and pairwise model-confidence estimates and predicted aligned errors. The initial release of AlphaFold DB contains over 360,000 predicted structures across 21 model-organism proteomes, which will soon be expanded to cover most of the (over 100 million) representative sequences from the UniRef90 data set.
Topics: Amino Acid Sequence; Animals; Bacteria; Databases, Protein; Datasets as Topic; Dictyostelium; Fungi; Humans; Internet; Models, Molecular; Plants; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Folding; Proteins; Software; Trypanosoma cruzi
PubMed: 34791371
DOI: 10.1093/nar/gkab1061 -
Cells Oct 2021The centrosome of amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin... (Review)
Review
The centrosome of amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin complexes. It is the major centrosomal model beyond animals and yeasts. Proteomics, protein interaction studies by BioID and superresolution microscopy methods led to considerable progress in our understanding of the composition, structure and function of this centrosome type. We discuss all currently known components of the centrosome in comparison to other centrosomes of animals and yeasts.
Topics: Cell Nucleus; Centrosome; Dictyostelium; Spindle Apparatus
PubMed: 34685637
DOI: 10.3390/cells10102657 -
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 -
Disease Models & Mechanisms Dec 2021The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are a group of neurological diseases that affect all ages and ethnicities worldwide.... (Review)
Review
The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are a group of neurological diseases that affect all ages and ethnicities worldwide. There are 13 different subtypes of NCL, each caused by a mutation in a distinct gene. The NCLs are characterized by the accumulation of undigestible lipids and proteins in various cell types. This leads to progressive neurodegeneration and clinical symptoms including vision loss, progressive motor and cognitive decline, seizures, and premature death. These diseases have commonly been characterized by lysosomal defects leading to the accumulation of undigestible material but further research on the NCLs suggests that altered protein secretion may also play an important role. This has been strengthened by recent work in biomedical model organisms, including Dictyostelium discoideum, mice, and sheep. Research in D. discoideum has reported the extracellular localization of some NCL-related proteins and the effects of NCL-related gene loss on protein secretion during unicellular growth and multicellular development. Aberrant protein secretion has also been observed in mammalian models of NCL, which has allowed examination of patient-derived cerebrospinal fluid and urine for potential diagnostic and prognostic biomarkers. Accumulated evidence links seven of the 13 known NCL-related genes to protein secretion, suggesting that altered secretion is a common hallmark of multiple NCL subtypes. This Review highlights the impact of altered protein secretion in the NCLs, identifies potential biomarkers of interest and suggests that future work in this area can provide new therapeutic insight.
Topics: Animals; Dictyostelium; Humans; Lysosomes; Mammals; Mice; Mutation; Neuronal Ceroid-Lipofuscinoses; Protein Transport; Sheep
PubMed: 34870700
DOI: 10.1242/dmm.049152 -
Microbial Biotechnology Jan 2021Dictyostelium discoideum is one of eight non-mammalian model organisms recognized by the National Institute of Health for the study of human pathology. The use of this... (Review)
Review
Dictyostelium discoideum is one of eight non-mammalian model organisms recognized by the National Institute of Health for the study of human pathology. The use of this slime mould is possible owing to similarities in cell structure, behaviour and intracellular signalling with mammalian cells. Its haploid set of chromosomes completely sequenced amenable to genetic manipulation, its unique and short life cycle with unicellular and multicellular stages, and phenotypic richness encoding many human orthologues, make Dictyostelium a representative and simple model organism to unveil cellular processes in human disease. Dictyostelium studies within the biomedical field have provided fundamental knowledge in the areas of bacterial infection, immune cell chemotaxis, autophagy/phagocytosis and mitochondrial and neurological disorders. Consequently, Dictyostelium has been used to the development of related pharmacological treatments. Herein, we review the utilization of Dictyostelium as a model organism in biomedicine.
Topics: Animals; Dictyostelium; Humans; Signal Transduction
PubMed: 33124755
DOI: 10.1111/1751-7915.13692