dictyNews
Electronic Edition
Volume 47, number 20
October 15, 2021
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Abstracts
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How phagocytes acquired the capability of hunting and removing
pathogens from a human body: lessons learned from chemotaxis
and phagocytosis of Dictyostelium discoideum
Xuehua Xu, Miao Pan and Tian Jin*
Chemotaxis Signaling Section, Laboratory of Immunogenetics,
NIAID, NIH, 5625 Fishers Lane, Rockville, MD 20852, USA.
*[log in to unmask]
Frontiers Cell Dev Biol, 9:724940.
How phagocytes find invading microorganisms and eliminate
pathogenic ones from human bodies is a fundamental question
in the study of infectious diseases. About 2.5 billion years ago,
eukaryotic unicellular organisms --protozoans-- appeared and
started to interact with various bacteria. Less than 1 billion years
ago, multicellular animals --metazoans-- appeared and acquired
the ability to distinguish self from non-self and to remove harmful
organisms from their bodies. Since then, animals have developed
innate immunity in which specialized white-blood cells -phagocytes-
patrol the body to kill pathogenic bacteria. The social amoebae
Dictyostelium discoideum are stereotypical phagocytes that chase
various bacteria via chemotaxis and consume them as food via
phagocytosis. Studies of this genetically amendable organism
have revealed evolutionarily conserved mechanisms underlying
chemotaxis and phagocytosis and shed light on studies of phagocytes
in mammals. In this review, we briefly summarize important studies
that contribute to our current understanding of how phagocytes
effectively find and kill pathogens via chemotaxis and phagocytosis.
submitted by: Xuehua Xu [[log in to unmask]]
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Membrane targeting of C2GAP1 enables Dictyostelium discoideum
to sense chemoattractant gradient at a higher concentration range
Xuehua Xu1a, Smit Bhimani1, Henderikus Pots2, Xi Wen1,
Taeck J. Jeon3, Arjan Kortholt2, and Tian Jin1
1Chemotaxis Signaling Section, Laboratory of Immunogenetics,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA
2Univeristy of Groningen, Nijenborgh 7, 9747 AG Groningen,
The Netherlands
3Department of Biology & BK21-Plus Research Team for Bioactive
Control Technology, College of Natural Sciences, Chosun University,
Gwangju 61452, Republic of Korea
aAuthor for correspondence: [log in to unmask]
Frontiers Cell Dev Biol, 9:725073.
Chemotaxis, which is G protein-coupled receptor (GPCR)-mediated
directional cell migration, plays pivotal roles in diverse human
diseases, including recruitment of leukocytes to inflammation sites
and metastasis of cancer. It is still not fully understood how eukaryotes
sense and chemotax in response to chemoattractants with an
enormous concentration range. A genetically traceable model organism,
Dictyostelium discoideum, is the best-studied organism for GPCR-
mediated chemotaxis. Recently, we have shown that C2GAP1 controls
G protein coupled receptor-mediated Ras adaptation and chemotaxis.
Here, we investigated the molecular mechanism and the biological
function of C2GAP1 membrane targeting for chemotaxis. We show
that calcium and phospholipids on the plasma membrane play critical
roles in membrane targeting of C2GAP1. Cells lacking C2GAP1
(c2gapA-) displayed an improved chemotaxis in response to
chemoattractant gradients at subsensitive or low concentrations
(<100 nM), while exhibiting impaired chemotaxis in response to
gradients at high concentrations (>1 microM). Taken together, our
results demonstrate that the membrane targeting of C2GAP1 enables
Dictyostelium to sense chemoattractant gradients at a higher
concentration range. This mechanism is likely an evolutionarily
conserved molecular mechanism of Ras regulation in the adaptation
and chemotaxis of eukaryotes.
submitted by: Xuehua Xu [[log in to unmask]]
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Visualizing Key Signaling Components of Macropinocytosis and
Phagocytosis using Confocal Microscopy in the Model Organism
Dictyostelium discoideum
Xuehua Xu1*, Joseph Brzostowski2, Sharmila Ramachandra1,
Smit Bhimani1, Yan You1, and Tian Jin1
1Chemotaxis Signaling Section, Laboratory of Immunogenetics,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, 5625 Fishers Lane, 4N03, Rockville,
MD 20852, USA.
2Twinbrook Imaging Facility, Laboratory of Immunogenetics,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, 5625 Fishers Lane, 4S06D, Rockville,
MD 20852, USA.
*Correspondence to: [log in to unmask]
Methods Mol Biol, Confocal Microscopy:
Methods and Protocols, 2304:193-205.
Macropinocytosis and phagocytosis are the processes by which
eukaryotic cells use their plasma membrane to engulf liquid or a
large particle and give rise to an internal compartment called the
macropinosomes or phagosome, respectively. Dictyostelium
discoideum provides a powerful system to understand the
molecular mechanism of these two fundamental cellular processes
that impact human health and disease. Recent developments in
fluorescence microscopy allow direct visualization of intracellular
signaling events with high temporal and spatial resolution. Here,
we describe methods to visualize temporospatial activation or
localization of key signaling components that are crucial for
macropinocytosis and phagocytosis using confocal
fluorescence microscopy.
submitted by: Xuehua Xu [[log in to unmask]]
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Altered protein secretion in Batten disease
Robert J. Huber
Department of Biology, Trent University, Peterborough, Ontario,
Canada
Disease Models & Mechanisms, accepted
The neuronal ceroid lipofuscinoses (NCLs), collectively known
as Batten disease, are a group of neurological disorders 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 disorders have classically been characterized by
lysosomal defects leading to the accumulation of undigestible
material but recent 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 7 of the 13
known NCL-related genes to protein secretion, suggesting that
altered secretion may be 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 may provide new
therapeutic insight.
submitted by: Robert Huber [[log in to unmask]]
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[End dictyNews, volume 47, number 20]
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