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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 -
FEMS Immunology and Medical Microbiology Jun 2007Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia... (Review)
Review
Among the many genera of free-living amoebae that exist in nature, members of only four genera have an association with human disease: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri and Sappinia diploidea. Acanthamoeba spp. and B. mandrillaris are opportunistic pathogens causing infections of the central nervous system, lungs, sinuses and skin, mostly in immunocompromised humans. Balamuthia is also associated with disease in immunocompetent children, and Acanthamoeba spp. cause a sight-threatening infection, Acanthamoeba keratitis, mostly in contact-lens wearers. Of more than 30 species of Naegleria, only one species, N. fowleri, causes an acute and fulminating meningoencephalitis in immunocompetent children and young adults. In addition to human infections, Acanthamoeba, Balamuthia and Naegleria can cause central nervous system infections in animals. Because only one human case of encephalitis caused by Sappinia diploidea is known, generalizations about the organism as an agent of disease are premature. In this review we summarize what is known of these free-living amoebae, focusing on their biology, ecology, types of disease and diagnostic methods. We also discuss the clinical profiles, mechanisms of pathogenesis, pathophysiology, immunology, antimicrobial sensitivity and molecular characteristics of these amoebae.
Topics: Acanthamoeba; Amebiasis; Amoeba; Animals; Humans; Naegleria fowleri
PubMed: 17428307
DOI: 10.1111/j.1574-695X.2007.00232.x -
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 -
Philosophical Transactions of the Royal... Feb 2019In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents... (Review)
Review
In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
Topics: Amoebozoa; Animals; Biological Evolution; Humans; Pinocytosis; Signal Transduction
PubMed: 30967007
DOI: 10.1098/rstb.2018.0158 -
Pathogens and Global Health Mar 2022Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis...
Pathogenic free-living amoebae affecting the central nervous system are known to cause granulomatous amoebic encephalitis (GAE) or primary amoebic meningoencephalitis (PAM). Although hosts with impaired immunity are generally at a higher risk of severe disease, amoebae such as and can instigate disease in otherwise immunocompetent individuals, whereas species mostly infect immunocompromised people. also cause a sight-threatening eye infection, mostly in contact lens wearers. Although infections due to pathogenic amoebae are considered rare, recently, these deadly amoebae were detected in water supplies in the USA. This is of particular concern, especially with global warming further exacerbating the problem. Herein, we describe the epidemiology, presentation, diagnosis, and management of free-living amoeba infections.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34602025
DOI: 10.1080/20477724.2021.1985892 -
Revista Chilena de Infectologia :... 2018
Topics: Amoeba; Humans; Peru
PubMed: 31095187
DOI: 10.4067/S0716-10182018000600669 -
Methods in Molecular Biology (Clifton,... 2013The model organism Dictyostelium discoideum is a member of the Amoebozoa, one of the six major -divisions of eukaryotes. Amoebozoa comprise a wide variety of amoeboid...
The model organism Dictyostelium discoideum is a member of the Amoebozoa, one of the six major -divisions of eukaryotes. Amoebozoa comprise a wide variety of amoeboid and flagellate organisms with single cells measuring from 5 μm to several meters across. They have adopted many different life styles and sexual behaviors and can live in all but the most extreme environments. This chapter provides an overview of Amoebozoan diversity and compares roads towards multicellularity within the Amoebozoa with inventions of multicellularity in other protist divisions. The chapter closes with a scenario for the evolution of Dictyostelid multicellularity from an Amoebozoan stress response.
Topics: Amoebozoa; Biological Evolution; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dictyostelium; Morphogenesis; Phylogeny; Protozoan Proteins; Signal Transduction; Spores, Protozoan
PubMed: 23494299
DOI: 10.1007/978-1-62703-302-2_1 -
Scientific Reports Jul 2022Coronamoeba villafranca gen. nov. sp. nov. is a small amoeba isolated from the surface planktonic biotope in the Bay of Villefranche (Mediterranean Sea). It has a...
Coronamoeba villafranca gen. nov. sp. nov. is a small amoeba isolated from the surface planktonic biotope in the Bay of Villefranche (Mediterranean Sea). It has a confusing set of morphological and molecular characters. Its locomotive form is subcylindrical and monopodial with monoaxial cytoplasmic flow and occasional hyaline bulging at the anterior edge (a monotactic morphotype). Based on this set of characters, this amoeba is most similar to members of the genus Nolandella (Tubulinea, Euamoebida). However, molecular phylogenetic analysis based on only the small subunit ribosomal RNA (SSU rRNA) gene and on two concatenated markers (SSU rRNA gene and actin) robustly places this species in the Discosea, specifically, in a clade with Dermamoeba and Paradermamoeba (Dermamoebida) as the closest described relatives, and several SSU rRNA clones from environmental DNA. A unique glycocalyx of the studied amoeba consisting of complex separate units with pentameric symmetry may be considered a unifying character of this species with other dermamoebids. The monotactic morphotype demonstrated by these amoebae primarily occurs in Tubulinea but was recently confirmed in other clades of Amoebozoa (e.g. Dactylopodida and Variosea). This morphotype may be the plesiomorphic mode of cell organization in Amoebozoa that might have evolved in the last amoebozoan common ancestor (LACA) and conserved in several lineages of this group. It may reflect basic characteristics of the cytoskeletal structure and functions in Amoebozoa.
Topics: Amoeba; Amoebozoa; Lobosea; Mediterranean Sea; Phylogeny
PubMed: 35869259
DOI: 10.1038/s41598-022-16721-2 -
International Journal of Molecular... Feb 2022Human dipeptidyl peptidase I (DPPI) belongs to the family of papain-like cysteine peptidases. Its distinctive features are the unique exclusion domain which enables the...
Human dipeptidyl peptidase I (DPPI) belongs to the family of papain-like cysteine peptidases. Its distinctive features are the unique exclusion domain which enables the eponymous activity and homotetramerization of DPPI, and its dependence on chloride ions for enzymatic activity. The oligomeric state of DPPI is unique in this family of predominantly monomeric peptidases. However, a distant DPPI ortholog from has been shown to be monomeric, indicating that the oligomeric state of DPPI varies between lineages. The aim of this work was to study the evolution of DPPI, with particular attention to the structural features that determine its characteristic enzymatic activity and preferences, and to reconstruct the evolution of its oligomerization. We analyzed fifty-seven selected sequences of DPPI and confirmed its presence in three lineages, namely, Amorphea (including animals and Amoebozoa), Alveolates and the metamonad . The amino acid residues that bind the chloride ion are highly conserved in all species, indicating that the dependence on chloride ions for activity is an evolutionarily conserved feature of DPPI. The number of N-glycosylation sites is significantly increased in animals, particularly vertebrates. Analysis of homology models and subunit contacts suggests that oligomerization is likely restricted to DPPIs in the Amorphea group.
Topics: Alveolata; Amoebozoa; Cathepsin C; Evolution, Molecular; Giardia; Glycosylation; Humans; Models, Molecular; Phylogeny; Protein Conformation; Protein Multimerization; Structural Homology, Protein
PubMed: 35163774
DOI: 10.3390/ijms23031852 -
Journal of Clinical Microbiology Jan 2022Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found...
Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found in water and soil worldwide. spp. and B. mandrillaris cause granulomatous amoebic encephalitis (GAE), which usually presents as a mass, while N. fowleri causes primary amoebic meningoencephalitis (PAM). spp. can also cause keratitis, and both spp. and can cause lesions in skin and respiratory mucosa. These amoebae can be difficult to diagnose clinically as these infections are rare and, if not suspected, can be misdiagnosed with other more common diseases. Microscopy continues to be the key first step in diagnosis, but the amoeba can be confused with macrophages or other infectious agents if an expert in infectious disease pathology or clinical microbiology is not consulted. Although molecular methods can be helpful in establishing the diagnosis, these are only available in referral centers. Treatment requires combination of antibiotics and antifungals and, even with prompt diagnosis and treatment, the mortality for neurological disease is extremely high.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Humans; Naegleria fowleri
PubMed: 34133896
DOI: 10.1128/JCM.00228-21