dictyNews
Electronic Edition
Volume 44, number 34
December 21, 2018
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to [log in to unmask]
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
=========
Cooperative predation in the social amoebae Dictyostelium discoideum
Michelle Rubin, Amber D. Miller, Mariko Katoh-Kurasawa, Christopher
Dinh, Adam Kuspa and Gad Shaulsky
Baylor College of Medicine, Houston, TX, USA
PLoS One, in press
The eukaryotic amoeba Dictyostelium discoideum is commonly used
to study sociality. The amoebae cooperate during development,
exhibiting altruism, cheating, and kin-discrimination, but growth while
preying on bacteria has been considered asocial. Here we show that
Dictyostelium are cooperative predators. Using mutants that grow
poorly on Gram-negative bacteria but grow well on Gram-positive
bacteria, we show that growth depends on cell-density and on prey
type. We also found synergy, by showing that pairwise mixes of
different mutants grow well on live Gram-negative bacteria. Moreover,
wild-type amoebae produce diffusible factors that facilitate mutant
growth and some mutants exploit the wild type in mixed cultures.
Finding cooperative predation in D. discoideum should facilitate studies
of this fascinating phenomenon, which has not been amenable to
genetic analysis before.
submitted by: Gad Shaulsky [[log in to unmask]]
——————————————————————————————————————
Akt and SGK 1 protein kinases are required for efficient feeding by
macropinocytosis
Thomas D. Williams, Sew-Yeu Peak-Chew, Peggy Paschke &
Robert R. Kay
MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK
J Cell Science, in press
Macropinocytosis is an actin-driven process of large-scale, non-specific
fluid uptake used for feeding by some cancer cells and the
macropinocytosis model organism Dictyostelium discoideum. In
Dictyostelium, macropinocytic cups are organised by ‘macropinocytic
patches’ in the plasma membrane. These contain activated Ras, Rac
and PI(3,4,5)P3 and direct actin polymerisation to their periphery. We
show that an Akt (PkbA) and an SGK (PkbR1) protein kinase act
downstream of PI(3,4,5)P3 and are together nearly essential for fluid
uptake. This pathway enables the formation of larger macropinocytic
patches and macropinosomes, thereby dramatically increasing fluid
uptake. Through phosphoproteomics, we identify a RhoGAP, GacG, as
a PkbA/PkbR1 target and show it is required for efficient
macropinocytosis and expansion of macropinocytic patches. The
function of Akt and SGK in cell feeding through control of
macropinosome size has implications for cancer cell biology
submitted by: Rob Kay [[log in to unmask]]
——————————————————————————————————————
The atypical MAP kinase ErkB transmits distinct chemotactic signals
through a core signalling module.
John M. E. Nichols1,2,6,7, Peggy Paschke1,6, Sew Peak-Chew1,
Thomas D. Williams1, Luke Tweedy3, Mark Skehel1, Elaine Stephens1,4,
Jonathan R. Chubb5, Robert R. Kay1
1. Cell Biology Division, MRC Laboratory of Molecular Biology,
Francis Crick Avenue, Cambridge, UK, CB2 0QH
2. MRC Laboratory for Molecular Cell Biology, University College London,
Gower St, London, UK, WC1E 6BT
3. Cancer Research UK Beatson Institute Glasgow, Bearsden, Glasgow,
UK, G61 1BD
4. Pfizer Inc, 1 Burtt Road, Andover, MA, USA
5. MRC Laboratory for Molecular Cell Biology and Department of Cell and
Developmental Biology, University College London, Gower St, London,
UK, WC1E 6BT
6. Authors contributed equally to this work
Dev. Cell, in press
Signalling from chemoattractant receptors activates the cytoskeleton of
crawling cells for chemotaxis. We show using phosphoproteomics that
different chemoattractants cause phosphorylation of the same core set of
around 80 proteins in Dictyostelium cells. Strikingly, the majority of these
are phosphorylated at an [S/T]PR motif by the atypical MAP kinase ErkB.
Unlike most chemotactic responses, ErkB phosphorylations are persistent
and do not adapt to sustained stimulation with chemoattractant. ErkB
integrates dynamic autophosphorylation with chemotactic signalling through
G-protein coupled receptors. Downstream, our phosphoproteomics data
defines a broad panel of regulators of chemotaxis. Surprisingly, targets are
almost exclusively other signalling proteins, rather than cytoskeletal
components, revealing ErkB as a regulator of regulators rather than acting
directly on the motility machinery. ErkB null cells migrate slowly and
orientate poorly over broad dynamic ranges of chemoattractant. Our data
indicate a central role for ErkB and its substrates in directing chemotaxis.
submitted by: Rob Kay [[log in to unmask]]
——————————————————————————————————————
Dictyostelium: an important source of structural and functional diversity
in drug discovery
Yuzuru Kubohara 1,* and Haruhisa Kikuchi 2
1 Laboratory of Health and Life Science, Graduate School of Health and
Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan
2 Laboratory of Natural Product Chemistry, Graduate School of
Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki,
Aoba-ku, Sendai 980-8578, Japan
* Correspondence
Cells, in press
The cellular slime mold Dictyostelium discoideum is an excellent model
organism for the study of cell and developmental biology because of its simple
life cycle and ease of use. Recent findings suggest that Dictyostelium, and
possibly other genera of cellular slime molds, are potential sources of novel
lead compounds for pharmacological and medical research. In this review, we
present supporting evidence that cellular slime molds are an untapped source
of lead compounds by examining the discovery and functions of polyketide
differentiation-inducing factor-1, a compound that was originally isolated as an
inducer of stalk-cell differentiation in D. discoideum and, together with its
derivatives, is now a promising lead compound for drug discovery in several
areas. We also review other novel compounds, including secondary metabolites,
that have been isolated from cellular slime molds.
submitted by: Yuzuru Kubohara [[log in to unmask]]
==============================================================
[End dictyNews, volume 44, number 34]
|
