dictyNews
Electronic Edition
Volume 47, number 4
February 5, 2021
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Abstracts
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Adenine Nucleotide Translocase regulates airway epithelial
metabolism, surface hydration, and ciliary function
Corrine R. Kliment1,2,3*, Jennifer M. K. Nguyen2,4, Mary Jane
Kaltreider3, YaWen Lu5, Steven M. Claypool5, Josiah E. Radder3,
Frank C. Sciurba3, Yingze Zhang3, Alyssa D. Gregory3, Pablo A.
Iglesias6, Venkataramana K. Sidhaye2,8 and Douglas N.
Robinson1,2,4,7*
1Department of Cell Biology, Johns Hopkins University School of
Medicine
2Department of Medicine, Division of Pulmonary and Critical Care,
Johns Hopkins University School of Medicine
3Department of Medicine, Division of Pulmonary and Critical Care,
University of Pittsburgh, Pittsburgh, PA 15260.
4Department of Pharmacology and Molecular Sciences, Johns
Hopkins University School of Medicine
5Department of Physiology, Johns Hopkins University School of
Medicine
6Department of Electrical and Computer Engineering Johns Hopkins
University.
7Chemical and Biomolecular Engineering, Johns Hopkins University,
Baltimore, MD 21205
8Department of Environmental Health Sciences and Engineering,
Johns Hopkins University School of Public Health
*Correspondence should be addressed to: Corrine Kliment,
[log in to unmask] and Douglas Robinson, [log in to unmask]
J. Cell Sci. 2021, in press
Airway hydration and ciliary function are critical to airway
homeostasis and dysregulated in chronic obstructive lung disease.
COPD is impacted by cigarette smoking with no therapeutic options.
We utilized a high copy cDNA library genetic selection approach in
the amoeba Dictyostelium discoideum to identify genetic protectors
from cigarette smoke (CS). Adenine nucleotide translocase, a
mitochondrial ADP/ATP transporter, was protective against CS in
Dictyostelium and human bronchial epithelial cells. ANT2 gene
expression is reduced in lung tissue from COPD patients and in a
mouse smoking model. ANT1 and ANT2 overexpression resulted in
enhanced oxidative respiration and ATP flux. In addition to ANT’s
presence in the mitochondria, ANT resides at the plasma membrane
in airway epithelial cells and regulates airway homeostasis. ANT2
overexpression stimulates airway surface hydration by ATP and
maintains ciliary beating after CS exposure, which are key
functions of the airway. Our study highlights the potential of ANT
upregulation and/or agonists in protecting from dysfunctional
mitochondrial metabolism, airway hydration, and ciliary motility
in COPD.
submitted by: Doug Robinson [[log in to unmask]]
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Cell dispersal by localized degradation of a chemoattractant
Richa Karmakar, Timothy Tyree, Richard H. Gomer, and
Wouter-Jan Rappel
PNAS February 9, 2021 118 (6) e2008126118
Chemotaxis, the guided motion of cells by chemical gradients, plays
a crucial role in many biological processes. In the social amoeba
Dictyostelium discoideum, chemotaxis is critical for the formation
of cell aggregates during starvation. The cells in these aggregates
generate a pulse of the chemoattractant, cyclic adenosine 3’,5’-
monophosphate (cAMP), every 6 min to 10 min, resulting in
surrounding cells moving toward the aggregate. In addition to
periodic pulses of cAMP, the cells also secrete phosphodiesterase
(PDE), which degrades cAMP and prevents the accumulation of the
chemoattractant. Here we show that small aggregates of Dictyostelium
can disperse, with cells moving away from instead of toward the
aggregate. This surprising behavior often exhibited oscillatory
cycles of motion toward and away from the aggregate. Furthermore,
the onset of outward cell motion was associated with a doubling of
the cAMP signaling period. Computational modeling suggests that this
dispersal arises from a competition between secreted cAMP and PDE,
creating a cAMP gradient that is directed away from the aggregate,
resulting in outward cell motion. The model was able to predict the
effect of PDE inhibition as well as global addition of exogenous
PDE, and these predictions were subsequently verified in
experiments. These results suggest that localized degradation of
a chemoattractant is a mechanism for morphogenesis.
submitted by: Wouter-Jan Rappel [[log in to unmask]]
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A proteomics analysis of calmodulin-binding proteins in
Dictyostelium discoideum during the transition from unicellular
growth to multicellular development
William D. Kim 1, Shyong Q. Yap 1 and Robert J. Huber 2
1 Environmental and Life Sciences Graduate Program, Trent
University, Peterborough, Ontario, Canada
2 Department of Biology, Trent University, Peterborough, Ontario,
Canada
International Journal of Molecular Sciences, accepted
Special Issue: Calmodulin Binding Proteins
Calmodulin (CaM) is an essential calcium-binding protein within
eukaryotes. CaM binds to calmodulin-binding proteins (CaMBPs)
and influences a variety of cellular and developmental processes. In
this study, we used immunoprecipitation coupled with mass
spectrometry (LC-MS/MS) to reveal over 500 putative CaM interactors
in the model organism Dictyostelium discoideum. Our analysis
revealed several known CaMBPs in Dictyostelium and mammalian
cells (e.g., myosin, calcineurin), as well as many novel interactors
(e.g., cathepsin D). GO term enrichment and STRING analyses linked
the CaM interactors to several cellular and developmental processes
in Dictyostelium including cytokinesis, gene expression,
endocytosis, and metabolism. The primary localizations of the CaM
interactors include the nucleus, ribosomes, vesicles, mitochondria,
cytoskeleton, and extracellular space. These findings are not only
consistent with previous work on CaM and CaMBPs in Dictyostelium,
but they also provide new insight on their diverse cellular and
developmental roles in this model organism. In total, this study
provides the first in vivo catalogue of putative CaM interactors in
Dictyostelium and sheds additional light on the essential roles of
CaM and CaMBPs in eukaryotes.
submitted by: Robert Huber[[log in to unmask]]
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