Copy Link
Add to Bookmark
Report
dictyNews Volume 37 Number 17
dictyNews
Electronic Edition
Volume 37, number 17
December 23, 2011
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to dicty@northwestern.edu
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
Back issues of dictyNews, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.
Follow dictyBase on twitter:
http://twitter.com/dictybase
=========
Abstracts
=========
Understanding the Cooperative Interaction between Myosin II and Actin
Crosslinkers Mediated by Actin Filaments during Mechanosensation
Tianzhi Luo,1, Krithika Mohan,3 Vasudha Srivastava,1,4 Yixin Ren,1
Pablo A. Iglesias,3 and Douglas N. Robinson1,2,4
1 Department of Cell Biology and 2 Department of Pharmacology and
Molecular Science, School of Medicine, Johns Hopkins University,
Baltimore, MD, 21205, USA
3 Department of Electrical and Computer Engineering and 4 Department
of Chemical and Biomolecular Engineering, Whiting School of Engineering,
Johns Hopkins University, Baltimore, MD, 21218, USA
Biophysical Journal, in press
Myosin II is a central mechanoenzyme in a wide range of cellular morphogenic
processes. Its cellular localization is dependent not only on signal transduction
pathways, but also on mechanical stress. We suggest that this stress-dependent
distribution is the result of both the force-dependent binding to actin filaments and
cooperative interactions between bound myosin heads. By assuming that the
binding of myosin heads induces and/or stabilizes local conformational changes
in the actin filaments which enhances myosin II binding locally, we successfully
simulate the cooperative binding of myosin to actin observed experimentally. In
addition, we can interpret the cooperative interactions between myosin and
actin-crosslinking proteins observed in cellular mechanosensation, provided that
a similar mechanism operates among different proteins. Finally, we present a
model that couples cooperative interactions to the assembly dynamics of myosin
bipolar thick filaments and that accounts for the transient behaviors of the
myosin II accumulation during mechanosensation. This mechanism is likely to be
general for a range of myosin II-dependent cellular mechanosensory processes.
Submitted by Doug Robinson [dnr@jhmi.edu>]
--------------------------------------------------------------------------------------
A New Biological Strategy for Drug Delivery: Eucaryotic Cell-Derived
Nanovesicles
Irne Tatischeff 1, Annette Alfsen2
1 Laboratoire Acides Nucliques et Biophotonique (CNRS, UPMC),
F-75252 Paris, France
2 CNRS UMR8104, INSERM, U567, Institut Cochin, Dpartement de Biologie
Cellulaire, Universit Paris-Descartes, F-75014 Paris, France
Journal of Biomaterials and Nanobiotechnology,
Special Issue on Drug Delivery, in press.
An efficient drug delivery is the prerequisite of the successful chemotherapeutic
treatments of many human diseases. Despite a great number of approaches,
the improvement of drug cell internalization remains an actual research challenge.
We propose a new biological delivery system based on the extracellular vesicles
released by a non-pathological eukaryotic microorganism, Dictyostelium discoideum.
After a summary of the main characteristics of these extracellular vesicles, including
of their lipid bilayer that appears as a good candidate for initiating membrane fusion,
followed by delivery of their encapsulated drug, the capacity of these vesicles to
convey drugs into human cells was demonstrated in vitro on two tumor cell lines,
resistant leukaemia K562r and cervix carcinoma HeLa cells. A comparison with
other extracellular vesicles, like exosomes or bacteria-derived particles, stresses
the unique properties of Dictyostelium extracellular nanovesicles for drug delivery.
Submitted by Irene Tatischeff [irene.tatischeff@upmc.fr]
--------------------------------------------------------------------------------------
Pleiotropic Roles of a Ribosomal Protein in Dictyostelium discoideum
Smita Amarnath 1, Trupti Kawli 1, Smita Mohanty 3, Narayanaswamy
Srinivasan 3 and Vidyanand Nanjundiah 2
1Joint first authors; e-mail: smita-nms@mail.utexas.edu and trupti@stanford.edu)
2Department of Molecular Reproduction, Development and Genetics
3 Molecular Biophysics Unit,
Indian Institute of Science, Bangalore 560012, INDIA
PLOS One, accepted
When expressed in Saccharomyces cerevisiae, a D. discoideum cDNA that
encodes the ribosomal protein S4 (DdS4) can rescue the phenotypic effects
of mutations in three cell cycle genes. The products of the genes in question,
cdc24, cdc42 and bem-1, affect morphogenesis in yeast via a coordinated
moulding of the cytoskeleton during bud site selection. Computational analysis
and mutational studies indicate how this might be achieved: an SH3 domain in
the yeast scaffold protein Bem-1p is central to constructing the bud site selection
complex, and a C-terminal domain in DdS4 is the functional equivalent of the
SH3 domain. In D. discoideum itself, cells that over- or under-express DdS4 do
not show detectable changes in protein synthesis. However, they display
developmental aberrations that are both similar and graded according to the
extent of over- or under-expression. This suggested to us that DdS4 might
influence morphogenesis via a stoichiometric effect Ð specifically, by taking
part in a multimeric complex similar to the one involving Cdc24p, Cdc42p and
Bem-1p in yeast. In support of the hypothesis, the S. cerevisiae proteins Cdc24p,
Cdc42p and Bem-1p as well as their D. discoideum cognates could be
co-precipitated with antibodies to DdS4. The implication is that DdS4 has at
least two functions in the cell. The first, vital, role is as part of the small subunit
of the ribosome. The second, ÔmoonlightingÕ, role of DdS4 is as part of another
multi-protein complex. An adaptation that (presumably) evolved for the second
role enables it fortuitously to rescue a set of cell cycle mutants in yeast. We
speculate that the second role acts as a built-in safeguard against the potentially
lethal consequences of sub-optimal ribosomal activity that might be caused by
spontaneous variations in DdS4 levels.
Submitted by Smita Amarnath [smita.smitar@gmail.com]
--------------------------------------------------------------------------------------
Colchicine affects cell motility, pattern formation and stalk cell differentiation
in Dictyostelium by altering calcium signaling
Yekaterina Poloz 1 and Danton H. O'Day 1,2
1 Department of Cell & Systems Biology, 25 Harbord Street, University of Toronto,
Toronto, ON, Canada M5S 3G5
2 Department of Biology, University of Toronto at Mississauga, 3359 Mississauga
Road Mississauga, ON, Canada L5L 1C6
Differentiation, in press
Previous work, verified here, showed that colchicine affects Dictyostelium pattern
formation, disrupts morphogenesis, inhibits spore differentiation and induces terminal
stalk cell differentiation. Here we show that colchicine specifically induces ecmB
expression and enhances accumulation of ecmB-expressing cells at the posterior
end of multicellular structures. Colchicine did not induce a nuclear translocation of
DimB, a DIF-1 responsive transcription factor in vitro. It also induced terminal stalk
cell differentiation in a mutant strain that does not produce DIF-1 (dmtA-) and after
the treatment of cells with DIF-1 synthesis inhibitor cerulenin (100 uM). This suggests
that colchicine induces the differentiation of ecmB-expressing cells independent of
DIF-1 production and likely through a signaling pathway that is distinct from the one
that is utilized by DIF-1. Depending on concentration, colchicine enhanced random
cell motility, but not chemotaxis, by 3-5 fold (10-50 mM colchicine, respectively)
through a Ca+2-mediated signaling pathway involving phospholipase C, calmodulin
and heterotrimeric G proteins. ColchicineÕs effects were not due to microtubule
depolymerization as other microtubule-depolymerizing agents did not have these
effects. Finally normal morphogenesis and stalk and spore cell differentiation of
cells treated with 10 mM colchicine were rescued through chelation of Ca+2 by
BAPTA-AM and EDTA and calmodulin antagonism by W-7 but not PLC inhibition
by U-73122. Morphogenesis or spore cell differentiation of cells treated with 50 mM
colchicine could not be rescued by the above treatments but terminal stalk cell
differentiation was inhibited by BAPTA-AM, EDTA and W-7, but not U-73122. Thus
colchicine disrupts morphogenesis and induces stalk cell differentiation through a
Ca+2-mediated signaling pathway involving specific changes in gene expression
and cell motility.
Submitted by Danton H. O'Day [danton.oday@utoronto.ca]
==============================================================
[End dictyNews, volume 37, number 17]
