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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 Journal of Cell Biology Sep 2023Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key...
Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI(3,5)P2-binding protein and characterize its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA, we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 3 min after engulfment but are then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P2.
Topics: Animals; Dictyostelium; Endosomes; Mammals; Phagosomes; Phosphatidylinositols; Phosphatidylinositol 3-Kinases
PubMed: 37382666
DOI: 10.1083/jcb.202209077 -
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 -
Current Opinion in Cell Biology Dec 2023Lamins are nuclear intermediate filament proteins with important, well-established roles in humans and other vertebrates. Lamins interact with DNA and numerous proteins... (Review)
Review
Lamins are nuclear intermediate filament proteins with important, well-established roles in humans and other vertebrates. Lamins interact with DNA and numerous proteins at the nuclear envelope to determine the mechanical properties of the nucleus, coordinate chromatin organization, and modulate gene expression. Many of these functions are conserved in the lamin homologs found in basal metazoan organisms, including Drosophila and Caenorhabditis elegans. Lamin homologs have also been recently identified in non-metazoans, like the amoeba Dictyostelium discoideum, yet how these proteins compare functionally to the metazoan isoforms is only beginning to emerge. A better understanding of these distantly related lamins is not only valuable for a more complete picture of eukaryotic evolution, but may also provide new insights into the function of vertebrate lamins.
Topics: Humans; Animals; Lamins; Dictyostelium; Nuclear Envelope; Drosophila; Intermediate Filament Proteins; Caenorhabditis elegans; Nuclear Lamina
PubMed: 37871500
DOI: 10.1016/j.ceb.2023.102267 -
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 -
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