dictyNews
Electronic Edition
Volume 42, number 4
February 5, 2016
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Abstracts
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Selective Localization of Myosin-I Proteins in Macropinosomes and
Actin Waves
Hanna Brzeska, Hilary Koech, Kevin J. Pridham, Edward D. Korn and
Margaret A. Titus
Cytoskeleton, in press
Class I myosins are widely expressed with roles in endocytosis and
cell migration in a variety of cell types. Dictyostelium express
multiple myosin Is, including three short-tailed (Myo1A, Myo1E,
Myo1F) and three long-tailed (Myo1B, Myo1C, Myo1D). Here we
report the molecular basis of the specific localizations of short-tailed
Myo1A, Myo1E and Myo1F compared to our previously determined
localization of long-tailed Myo1B. Myo1A and Myo1B have common
and unique localizations consistent with the various features of their
tail region; specifically the BH sites in their tails are required
for their association with the plasma membrane and heads are
sufficient for relocalization to the front of polarized cells. Myo1A
does not localize to actin waves and macropinocytic protrusions, in
agreement with the absence of a tail region which is required for
these localizations of Myo1B. However, in spite of the overall
similarity of their domain structures, the cellular distributions of
Myo1E and Myo1F are quite different from Myo1A. Myo1E and
Myo1F, but not Myo1A, are associated with macropinocytic cups and
actin waves. The localizations of Myo1E and Myo1F in macropinocytic
structures and actin waves differ from the localization of Myo1B.
Myo1B colocalizes with F-actin in the actin waves and at the tips of
mature macropinocytic cups whereas Myo1E and Myo1F are in the
interior of actin waves and along the entire surface of macropinocytic
cups. Our results point to different mechanisms of targeting of short-
and long-tailed myosin Is, and are consistent with these myosin’s
having both shared and divergent cellular functions.
submitted by: Hanna Brzeska [[log in to unmask]]
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Gbeta Regulates Coupling between ActinOscillators for Cell Polarity
and Directional Migration
Oliver Hoeller1, Jared E. Toettcher1, Huaqing Cai2, Yaohui Sun3,
Chuan-Hsiang Huang2, Mariel Freyre4, Min Zhao3, Peter N. Devreotes2,
Orion D. Weiner1*
PLOS Biology
For directional movement, eukaryotic cells depend on the proper
organization of their actin cytoskeleton. This engine of motility is
made up of highly dynamic nonequilibrium actin structures such as
flashes, oscillations, and traveling waves. In Dictyostelium, oscillatory
actin foci interact with signals such as Ras and phosphatidylinositol
3,4,5-trisphosphate (PIP3) to form protrusions. However, how signaling
cues tame actin dynamics to produce a pseudopod and guide cellular
motility is a critical open question in eukaryotic chemotaxis. Here, we
demonstrate that the strength of coupling between individual actin
oscillators controls cell polarization and directional movement. We
implement an inducible sequestration system to inactivate the
heterotrimeric G protein subunit Gbeta and find that this acute
perturbation triggers persistent, high-amplitude cortical oscillations
of F-actin. Actin oscillators that are normally weakly coupled to one
another in wild-type cells become strongly synchronized following
acute inactivation of Gbeta. This global coupling impairs sensing of
internalcues during spontaneous polarization and sensing of external
cues during directional motility. A simple mathematical model of
coupled actin oscillators reveals the importance of appropriate
coupling strength for chemotaxis: moderate coupling can increase
sensitivity to noisy inputs. Taken together, our data suggest that
Gbeta regulates the strength of coupling between actin oscillators
for efficient polarity and directional migration. As these observations
are only possible following acute inhibition of Gbeta and are masked
by slow compensation in genetic knockouts, our work also shows that
acute loss-of-function approaches can complement and extend the
reach of classical genetics in Dictyostelium and likely other systems
as well.
submitted by: Oliver Hoeller [[log in to unmask]]
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Identification of a chemoattractant G-protein-coupled receptor for
folic acid that controls both chemotaxis and phagocytosis
Miao Pan, Xuehua Xu, Yong Chen and Tian Jin
Developmental Cell, in press
Eukaryotic phagocytes search and destroy invading microorganisms via
chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum
is a professional phagocyte that chases bacteria through chemotaxis and
engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs)
are known for detecting chemoattractants and directing cell migration, but
their roles in phagocytosis are not clear. Here, we developed a quantitative
phosphoproteomic technique to discover signaling components. Using this
approach, we discovered the long-sought-after folic acid receptor, fAR1, in
D. discoideum. We showed that the seven transmembrane receptor fAR1
is required for folic acid-mediated signaling events. Significantly, we
discovered that fAR1 is essential for both chemotaxis and phagocytosis of
bacteria, thereby representing a chemoattractant GPCR that mediates not
only chasing but also ingesting bacteria. We revealed that a phagocyte is
able to internalize particles via chemoattractant-mediated engulfment process.
We propose that mammalian phagocytes may also use this mechanism to
engulf and ingest bacterial pathogens.
submitted by: Miao Pan [[log in to unmask]]
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[End dictyNews, volume 42, number 4]
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