scholarly journals Conserved actin machinery drives microtubule-independent motility and phagocytosis in Naegleria

2020 ◽  
Vol 219 (11) ◽  
Author(s):  
Katrina B. Velle ◽  
Lillian K. Fritz-Laylin
Keyword(s):  
Actin Cytoskeleton ◽  
Common Ancestor ◽  
Genomic Analysis ◽  
Model System ◽  
Human Cells ◽  
Eukaryotic Cells ◽  
Powerful System ◽  
Cell Crawling ◽  
Work Supports ◽  
The Brain

Much of our understanding of actin-driven phenotypes in eukaryotes has come from the “yeast-to-human” opisthokont lineage and the related amoebozoa. Outside of these groups lies the genus Naegleria, which shared a common ancestor with humans >1 billion years ago and includes the “brain-eating amoeba.” Unlike nearly all other known eukaryotic cells, Naegleria amoebae lack interphase microtubules; this suggests that actin alone drives phenotypes like cell crawling and phagocytosis. Naegleria therefore represents a powerful system to probe actin-driven functions in the absence of microtubules, yet surprisingly little is known about its actin cytoskeleton. Using genomic analysis, microscopy, and molecular perturbations, we show that Naegleria encodes conserved actin nucleators and builds Arp2/3–dependent lamellar protrusions. These protrusions correlate with the capacity to migrate and eat bacteria. Because human cells also use Arp2/3–dependent lamellar protrusions for motility and phagocytosis, this work supports an evolutionarily ancient origin for these processes and establishes Naegleria as a natural model system for studying microtubule-independent cytoskeletal phenotypes.

scholarly journals Arp2/3 complex-mediated actin assembly drives microtubule-independent motility and phagocytosis in the evolutionarily divergent amoeba Naegleria

2020 ◽  
Author(s):  
Katrina B. Velle ◽  
Lillian K. Fritz-Laylin
Keyword(s):  
Actin Cytoskeleton ◽  
Common Ancestor ◽  
Genomic Analysis ◽  
Eukaryotic Cell ◽  
Model System ◽  
Human Cells ◽  
Actin Assembly ◽  
Cell Type ◽  
Cytoplasmic Microtubules ◽  
Work Supports

ABSTRACTMuch of our current understanding of actin-driven phenotypes in eukaryotes has come from the “yeast to human” opisthokont lineage, as well as the related amoebozoa. Outside of these groups lies the genus Naegleria, which shared a common ancestor with humans over a billion years ago, and includes the deadly “brain-eating amoeba.” Unlike nearly every other known eukaryotic cell type, Naegleria amoebae are thought to lack cytoplasmic microtubules. The absence of microtubules suggests that these amoebae rapidly crawl and phagocytose bacteria using actin alone. Although this makes Naegleria a powerful system to probe actin-driven functions in the absence of microtubules, surprisingly little is known about Naegleria’s actin cytoskeleton. Here, we use microscopy and genomic analysis to show that Naegleria amoebae have an extensive actin cytoskeletal repertoire, complete with nucleators and nucleation promoting factors. Naegleria use this cytoskeletal machinery to generate Arp2/3-dependent lamellar protrusions, which correlate with the capacity to migrate and phagocytose bacteria. Because human cells also use Arp2/3-dependent lamellar protrusions for motility and phagocytosis, this work supports an evolutionarily ancient origin for these actin-driven processes and establishes Naegleria as a natural model system for studying microtubule-independent cytoskeletal phenotypes.

Measuring the World

2018 ◽  
Author(s):  
Ann-Sophie Barwich
Keyword(s):  
Sensory Information ◽  
Network Models ◽  
Model System ◽  
Stimulus Input ◽  
Expectancy Effects ◽  
Neural Network Models ◽  
Perceptual Object ◽  
External Objects ◽  
The Common ◽  
The Brain

How much does stimulus input shape perception? The common-sense view is that our perceptions are representations of objects and their features and that the stimulus structures the perceptual object. The problem for this view concerns perceptual biases as responsible for distortions and the subjectivity of perceptual experience. These biases are increasingly studied as constitutive factors of brain processes in recent neuroscience. In neural network models the brain is said to cope with the plethora of sensory information by predicting stimulus regularities on the basis of previous experiences. Drawing on this development, this chapter analyses perceptions as processes. Looking at olfaction as a model system, it argues for the need to abandon a stimulus-centred perspective, where smells are thought of as stable percepts, computationally linked to external objects such as odorous molecules. Perception here is presented as a measure of changing signal ratios in an environment informed by expectancy effects from top-down processes.

Mammalian mitochondrial translation — revealing consequences of divergent evolution

2019 ◽  
Vol 47 (5) ◽  
pp. 1429-1436 ◽  
Author(s):  
Rawaa A. Z. Al-Faresi ◽  
Robert. N. Lightowlers ◽  
Zofia M. A. Chrzanowska-Lightowlers
Keyword(s):  
Common Ancestor ◽  
Current Knowledge ◽  
Eukaryotic Cells ◽  
Divergent Evolution ◽  
Mitochondrial Translation ◽  
Complete Understanding ◽  
Genetic Origin ◽  
Cryo Electron Microscopy ◽  
Encoded Proteins ◽  
Molecular Aspects

Abstract Mitochondria are ubiquitous organelles present in the cytoplasm of all nucleated eukaryotic cells. These organelles are described as arising from a common ancestor but a comparison of numerous aspects of mitochondria between different organisms provides remarkable examples of divergent evolution. In humans, these organelles are of dual genetic origin, comprising ∼1500 nuclear-encoded proteins and thirteen that are encoded by the mitochondrial genome. Of the various functions that these organelles perform, it is only oxidative phosphorylation, which provides ATP as a source of chemical energy, that is dependent on synthesis of these thirteen mitochondrially encoded proteins. A prerequisite for this process of translation are the mitoribosomes. The recent revolution in cryo-electron microscopy has generated high-resolution mitoribosome structures and has undoubtedly revealed some of the most distinctive molecular aspects of the mitoribosomes from different organisms. However, we still lack a complete understanding of the mechanistic aspects of this process and many of the factors involved in post-transcriptional gene expression in mitochondria. This review reflects on the current knowledge and illustrates some of the striking differences that have been identified between mitochondria from a range of organisms.

Evolution of vacuolar H+-ATPases: immunological relationships of the nucleotide-binding subunits

1989 ◽  
Vol 67 (6) ◽  
pp. 306-310 ◽  
Author(s):  
Morris F. Manolson ◽  
Judith M. Percy ◽  
David K. Apps ◽  
Xiao-Song Xie ◽  
Dennis K. Stone ◽  
...  
Keyword(s):  
Anaerobic Bacterium ◽  
Common Ancestor ◽  
Sequence Data ◽  
Structural Features ◽  
Eukaryotic Cells ◽  
Clostridium Pasteurianum ◽  
Chromaffin Granules ◽  
Α Subunit ◽  
Evolutionary Origins ◽  
Vacuolar Membranes

The evolution of the endomembrane systems of eukaryotic cells can be examined by exploring the evolutionary origins of the endomembrane H+-ATPases. Recent studies suggest that certain polypeptides are common to all H+ pumps of this type. Tonoplast H+ -ATPase from Beta vulgaris L. was purified and antibodies raised to two of its subunits. Each of these antisera reacted with a polypeptide of the corresponding size in bovine chromaffin granules, bovine clathrincoated vesicles, and yeast vacuolar membranes, suggesting common structural features and a common ancestor for endomembrane H+-ATPases of different organelles and different kingdoms. The antiserum raised against the 57-kDa polypeptide of plant tonoplast H+ -ATPase also reacted with subunit "a" of the H+-ATPase from the obligately anaerobic bacterium Clostridium pasteurianum and to the α subunit of the H+ -ATPase from Escherichia coli. There was no reactivity with chloroplast or mitochondrial ATPases. These results are discussed in relation to recent sequence data which suggest that endomembrane H+-ATPases may be evolutionarily related to the F0F1 ATPases.Key words: H+ -ATPase, evolution, immunology, vacuole, endomembrane.

Inductive patterning of the embryonic brain in Drosophila

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2121-2128
Author(s):  
Damon T. Page
Keyword(s):  
Brain Development ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Embryonic Brain ◽  
Germ Layers ◽  
Brain Anomaly ◽  
Prechordal Plate ◽  
Foregut Endoderm ◽  
The Brain ◽  
Brain Patterning

In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechanism of brain development occurs in the protostome Drosophila, and find that the foregut and mesoderm act to pattern the fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated, brain patterning is disrupted. The loss of Hedgehog expressed in the foregut appears to mediate this effect, as it does in vertebrates. One mechanism whereby these defects occur is a disruption of normal apoptosis in the brain. These data argue that the last common ancestor of protostomes and deuterostomes had a prototype of the brains present in modern animals, and also suggest that the foregut and mesoderm contributed to the patterning of this ‘proto-brain’. They also argue that the foreguts of protostomes and deuterostomes, which have traditionally been assigned to different germ layers, are actually homologous.

scholarly journals Talent in the taxi: a model system for exploring expertise

2009 ◽  
Vol 364 (1522) ◽  
pp. 1407-1416 ◽  
Author(s):  
Katherine Woollett ◽  
Hugo J. Spiers ◽  
Eleanor A. Maguire
Keyword(s):  
Model System ◽  
Neural Mechanisms ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Taxi Drivers ◽  
The Brain ◽  
Use Of Expertise ◽  
Widespread Interest ◽  
Key Questions ◽  
Extensive Practice

While there is widespread interest in and admiration of individuals with exceptional talents, surprisingly little is known about the cognitive and neural mechanisms underpinning talent, and indeed how talent relates to expertise. Because many talents are first identified and nurtured in childhood, it can be difficult to determine whether talent is innate, can be acquired through extensive practice or can only be acquired in the presence of the developing brain. We sought to address some of these issues by studying healthy adults who acquired expertise in adulthood. We focused on the domain of memory and used licensed London taxi drivers as a model system. Taxi drivers have to learn the layout of 25 000 streets in London and the locations of thousands of places of interest, and pass stringent examinations in order to obtain an operating licence. Using neuropsychological assessment and structural and functional magnetic resonance imaging, we addressed a range of key questions: in the context of a fully developed brain and an average IQ, can people acquire expertise to an exceptional level; what are the neural signatures, both structural and functional, associated with the use of expertise; does expertise change the brain compared with unskilled control participants; does it confer any cognitive advantages, and similarly, does it come at a cost to other functions? By studying retired taxi drivers, we also consider what happens to their brains and behaviour when experts stop using their skill. Finally, we discuss how the expertise of taxi drivers might relate to the issue of talent and innate abilities. We suggest that exploring talent and expertise in this manner could have implications for education, rehabilitation of patients with cognitive impairments, understanding individual differences and possibly conditions such as autism where exceptional abilities can be a feature.

Porcine endogenous retrovirus does not infect human cells using a bioartificial liver model system

2001 ◽  
Vol 33 (1-2) ◽  
pp. 1780-1781 ◽  
Author(s):  
E Falasca ◽  
V Adami ◽  
G Astori ◽  
A Donini ◽  
F Biffoni ◽  
...  
Keyword(s):  
Endogenous Retrovirus ◽  
Bioartificial Liver ◽  
Model System ◽  
Human Cells ◽  
Liver Model ◽  
Porcine Endogenous Retrovirus

Rho family GTPases

2012 ◽  
Vol 40 (6) ◽  
pp. 1378-1382 ◽  
Author(s):  
Alan Hall
Keyword(s):  
Actin Cytoskeleton ◽  
Rho Gtpases ◽  
Cellular Response ◽  
Molecular Switches ◽  
Effector Proteins ◽  
Eukaryotic Cells ◽  
Cell Behaviour ◽  
Wide Range ◽  
Rho Family Gtpases ◽  
Rho Family

Rho GTPases comprise a family of molecular switches that control signal transduction pathways in eukaryotic cells. A conformational change induced upon binding GTP promotes an interaction with target (effector) proteins to generate a cellular response. A highly conserved function of Rho GTPases from yeast to humans is to control the actin cytoskeleton, although, in addition, they promote a wide range of other cellular activities. Changes in the actin cytoskeleton drive many dynamic aspects of cell behaviour, including morphogenesis, migration, phagocytosis and cytokinesis, and the dysregulation of Rho GTPases is associated with numerous human diseases and disorders.

scholarly journals WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility

2017 ◽  
Vol 216 (6) ◽  
pp. 1673-1688 ◽  
Author(s):  
Lillian K. Fritz-Laylin ◽  
Samuel J. Lord ◽  
R. Dyche Mullins
Keyword(s):  
Actin Polymerization ◽  
Eukaryotic Cells ◽  
Human Neutrophils ◽  
Evolutionary Relationships ◽  
Actin Assembly ◽  
Complex Environments ◽  
Clear Trend ◽  
Cell Crawling ◽  
Evolutionarily Conserved ◽  
Underlying Mechanisms

Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call “α-motility.” Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE—activators of branched actin assembly—make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP’s role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin.

scholarly journals Cytoplasmic foci are sites of mRNA decay in human cells

2004 ◽  
Vol 165 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Nicolas Cougot ◽  
Sylvie Babajko ◽  
Bertrand Séraphin
Keyword(s):  
Mrna Decay ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Human Cells ◽  
Eukaryotic Cells ◽  
Mrna Turnover ◽  
Expression Control ◽  
Gene Expression Control ◽  
Cytoplasmic Structures

Understanding gene expression control requires defining the molecular and cellular basis of mRNA turnover. We have previously shown that the human decapping factors hDcp2 and hDcp1a are concentrated in specific cytoplasmic structures. Here, we show that hCcr4, hDcp1b, hLsm, and rck/p54 proteins related to 5′–3′ mRNA decay also localize to these structures, whereas DcpS, which is involved in cap nucleotide catabolism, is nuclear. Functional analysis using fluorescence resonance energy transfer revealed that hDcp1a and hDcp2 interact in vivo in these structures that were shown to differ from the previously described stress granules. Our data indicate that these new structures are dynamic, as they disappear when mRNA breakdown is abolished by treatment with inhibitors. Accumulation of poly(A)+ RNA in these structures, after RNAi-mediated inactivation of the Xrn1 exonuclease, demonstrates that they represent active mRNA decay sites. The occurrence of 5′–3′ mRNA decay in specific subcellular locations in human cells suggests that the cytoplasm of eukaryotic cells may be more organized than previously anticipated.

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