dictyNews
Electronic Edition
Volume 47, number 2
January 22, 2021
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Abstracts
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Kabra A and Kim L. 2020.
Superoxide Dismutase C affects Dictyostelium Contractile Vacuole
biogenesis and function.
Differentiation, Growth, and Development. 62(9):516-526
Dictyostelium cells cope with hypo-osmotic stress with a
Contractile Vacuole (CV) system, which consists of one or two
vacuoles that cyclically charge and discharge. Uniquely, a
F-Actin remodeling dependent minimal mixing of the CV membrane
components with the target plasmalemma during the fusion and the
dischargement warrants the integrity of the CV bladder for the
efficient next CV cycle (Heuser, 2006). The effect of hypo-osmotic
stress on F-Actin remodeling activity, however, is currently not
well understood. Dictyostelium cells increase the level of
intracellular superoxide level in response to hypo-osmotic stress,
which in turn activates redox sensitive Ras proteins, but not Akt,
which is one of the Ras downstream targets and a major regulator
of F-Actin remodeling. However, Akt is not insulated from the
active Ras in cells lacking Superoxide dismutase C (SodC). We
report here that sodC- cells were compromised in the CV structure
and function and the attenuation of Ras/PI3K/Akt signaling in
several independent means significantly improved the compromised
CV structure but not the function. Interestingly, when sodC-
cells were treated with 5-(N,N-Dimethyl) amiloride hydrochloride
(EIPA), an inhibitor of sodium proton exchanger (NHE), both the
structure and the function of the CV improved. Thus, a proper CV
biogenesis in sodC- cells was insufficient to restore their CV
function, which in turn indicates the presence of an additional
target for SodC and EIPA that modulates CV function.
submitted by: Lou Kim [[log in to unmask]]
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A hypothetical MEK1-MIP1-SMEK multiprotein signaling complex may
function in Dictyostelium and mammalian cells.
Alex Sobko
Int. J. Dev. Biol. Publication date 2020/10/20
In a previous study, we characterized Dictyostelium SUMO targeted
ubiquitin ligase (StUbL) MIP1 that associates with protein kinase
MEK1 and targets SUMOylated MEK1 to ubiquitination (Sobko et al.,
2002). These modifications happen in response to activation of
MEK1 by the chemoattractant cAMP. Second site genetic suppressor
of mek1-null phenotype (SMEK) was also identified in Dictyostelium.
MEK1 and SMEK belong to the same linear pathway, in which MEK1
negatively regulates SMEK, which then negatively regulates
chemotaxis and aggregation. RNF4 is mammalian homologue of MIP.
RNF4 interacts with hSMEK2, the human homologue of Dictyostelium
SMEK. We propose the existence of an evolutionarily conserved
MEK1-SMEK signaling complex that upon MEK1 activation and
SUMOylation, recruits ubiqutin ligase MIP1/RNF4, which, in turn,
ubiquitinates SMEK and targets this protein for proteasomal
degradation. This could be a mechanism for negative regulation
of SMEK by MEK1 signaling.
submitted by: Alex Sobko [[log in to unmask]]
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Unified control of amoeboid pseudopod extension in multiple organisms
by branched F-actin in the front and parallel F-actin/myosin in the cortex
Peter J.M. van Haastert
Department of Cell Biochemistry, University of Groningen,
the Netherlands
PLoS One, doi.org/10.1371/journal.pone.0243442
The trajectory of moving eukaryotic cells depends on the kinetics
and direction of extending pseudopods. The direction of pseudopods
has been well studied to unravel mechanisms for chemotaxis, wound
healing and inflammation. However, the kinetics of pseudopod
extension – when and why do pseudopods start and stop- is equally
important, but is largely unknown. Here the START and STOP of about
4000 pseudopods was determined in four different species, at four
conditions and in nine mutants (fast amoeboids Dictyostelium and
neutrophils, slow mesenchymal stem cells, and fungus B.d. chytrid
with pseudopod and a flagellum). The START of a first pseudopod is
a random event with a probability that is species-specific
(23%/s for neutrophils). In all species and conditions, the START of a
second pseudopod is strongly inhibited by the extending first
pseudopod, which depends on parallel filamentous actin/myosin in the
cell cortex. Pseudopods extend at a constant rate by polymerization
of branched F-actin at the pseudopod tip, which requires the Scar
complex. The STOP of pseudopod extension is induced by multiple
inhibitory processes that evolve during pseudopod extension and
mainly depend on the increasing size of the pseudopod. Surprisingly,
no differences in pseudopod kinetics are detectable between
polarized, unpolarized or chemotactic cells, and also not between
different species except for small differences in numerical values.
This suggests that the analysis has uncovered the fundament of cell
movement with distinct roles for stimulatory branched F-actin in the
protrusion and inhibitory parallel F-actin in the contractile cortex.
submitted by: Peter van Haastert [[log in to unmask]]
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Short- and long-term memory of moving amoeboid cells
Peter J.M. van Haastert
Department of Cell Biochemistry, University of Groningen,
the Netherlands
PLoS One, accepted
Amoeboid cells constantly change shape and extend protrusions.
The direction of movement is not random, but is correlated with the
direction of movement in the preceding minutes. The basis of this
correlation is an underlying memory of direction. The presence of
memory in movement is known for many decades, but its molecular
mechanism is still largely unknown. This study reports in detail on
the information content of directional memory, the kinetics of
learning and forgetting this information, and the molecular basis
for memory using Dictyostelium mutants. Two types of memory were
characterized. A short-term memory stores for ~20 seconds the position
of the last pseudopod using a local modification of the branched
F-actin inducer SCAR/WAVE, which enhances one new pseudopod to
be formed at the position of the previous pseudopod. A long term
memory stores for ~2 minutes the activity of the last ~10 pseudopods
using a cGMP-binding protein that induces myosin filaments in the rear
of the cell; this inhibits pseudopods in the rear and thereby enhances
pseudopods in the global front. Similar types of memory were
identified in human neutrophils and mesenchymal stem cells, the
protist Dictyostelium and the fungus B.d. chytrid. The synergy of
short- and long-term memory explains their role in persistent movement
for enhanced cell dispersal, food seeking and chemotaxis.
submitted by: Peter van Haastert [[log in to unmask]]
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Symmetry Breaking during Cell Movement in the Context of Excitability,
Kinetic Fine-Tuning and Memory of Pseudopod Formation
Peter J.M. van Haastert
Department of Cell Biochemistry, University of Groningen,
the Netherlands; [log in to unmask]
Cells, doi.org/10.3390/cells9081809 Essay
The path of moving eukaryotic cells depends on the kinetics and
direction of extending pseudopods. Amoeboid cells constantly change
their shape with pseudopods extending in different directions. Detailed
analysis has revealed that time, place and direction of pseudopod
extension are not random, but highly ordered with strong prevalence for
only one extending pseudopod, with defined life-times, and with
reoccurring events in time and space indicative of memory. Important
components are Ras activation and the formation of branched F-actin in
the extending pseudopod and inhibition of pseudopod formation in the
contractile cortex of parallel F-actin/myosin. In biology, order very
often comes with symmetry. In this essay, I discuss cell movement and
the dynamics of pseudopod extension from the perspective of symmetry
and symmetry changes of Ras activation and the formation of branched
F-actin in the extending pseudopod. Combining symmetry of Ras activation
with kinetics and memory of pseudopod extension results in a refined
model of amoeboid movement that appears to be largely conserved in the
fast moving Dictyostelium and neutrophils, the slow moving mesenchymal
stem cells and the fungus B.d. chytrid.
submitted by: Peter van Haastert [[log in to unmask]]
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[End dictyNews, volume 47, number 2]
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