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Dictybase Northwestern <[log in to unmask]>
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Fri, 12 Sep 2014 21:52:23 +0000
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dictyNews
Electronic Edition
Volume 40, number 23
September 12, 2014

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.

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=========
Abstracts
=========


The hybrid type polyketide synthase SteelyA is required for cAMP 
signalling in early Dictyostelium development

Takaaki B. Narita, Zhi-hui Chen, Pauline Schaap and Tamao Saito


PLoS One, in press

BACK GROUND: In our previous study we found that the expression 
of stlA showed peaks both in the early and last stages of development 
and that a product of SteelyA, 4-methyl-5-pentylbenzene-1,3-diol 
(MPBD), controlled Dictyostelium spore maturation during the latter. In 
this study we focused on the role of SteelyA in early stage development.

PRINCIPAL FINDINGS: Our stlA null mutant showed aggregation delay 
and abnormally small aggregation territories. Chemotaxis analysis 
revealed defective cAMP chemotaxis in stlA null mutant. cAMP 
chemotaxis was restored by MPBD addition during early stage 
development. Assay for cAMP relay response revealed that the stlA null 
mutant had lower cAMP accumulation during aggregation, suggesting 
lower ACA activity than the wild type strain. Exogenous cAMP pulses 
rescued the aggregation defect of the stlA null strain in the absence of 
MPBD. Expression analysis of cAMP signalling genes revealed lower 
expression levels in stlA null mutant during aggregation.

CONCLUSION: Our data indicate a regulatory function by SteelyA on 
cAMP signalling during aggregation and show that SteelyA is 
indispensable for ACA full induction.


Submitted by Tamao Saito [[log in to unmask]]
---------------------------------------------------------------------------


Vmp1 regulates PtdIns3P signaling during autophagosome formation 
in Dictyostelium discoideum

Javier Calvo-Garrido, Jason S. King, Sandra Muņoz-Braceras and 
Ricardo Escalante

Traffic, in press

Generation and turnover of PtdIns3P signaling is essential for 
autophagosome formation and other membrane traffic processes. 
In both Dictyostelium discoideum and mammalian cells, 
autophagosomes are formed from specialized regions of the 
endoplasmic reticulum (ER), called omegasomes, which are 
enriched in the signaling lipid PtdIns3P. Vmp1 is a multi-spanning 
membrane protein localized at the ER that is required for 
autophagosome formation. There are conflicting reports in the 
literature as to whether Vmp1 is strictly required or not for 
autophagy-related PtdIns3P signaling and its hierarchical 
relationship with Atg1 and PI3K. We have now addressed these 
questions in the Dictyostelium model.  We show that Dictyostelium 
cells lacking Vmp1 have elevated and aberrant PtdIns3P signaling 
on the ER, resulting in an increased and persistent recruitment of 
Atg18 and other autophagic proteins. This indicates that Vmp1 is 
not strictly essential for the generation of PtdIns3P signaling but 
rather suggests a role in the correct turnover or modulation of this 
signaling. Of interest, these PtdIns3P-enriched regions of the ER 
surround ubiquitinated protein aggregates but are unable to form 
functional autophagosomes. vmp1 null cells also have additional 
defects in macropinocytosis and growth, that are not shared by 
other autophagy mutants. Remarkably, we show that these defects 
and also the aberrant PtdIns3P distribution are largely suppressed 
by the concomitant loss of Atg1, indicating that aberrant autophagic 
signaling on the ER inhibits macropinocytosis. These results 
suggest that Atg1 functions upstream of Vmp1 in this signaling 
pathway and demonstrates a previously unappreciated link 
between abnormal autophagy signaling and macropinocytosis.


Submitted by Ricardo Escalante [[log in to unmask]]
---------------------------------------------------------------------------


Cellular memory in eukaryotic chemotaxis

Monica Skoge1,2 , Haicen Yue2 , Michael Erickstad2, Albert Bae1,2, 
Herbert Levine3, Alex Groisman2,   William F. Loomis1, and 
Wouter-Jan Rappel2

1 Department of Biology, University of California San Diego, 
La Jolla, CA 92093
2 Department of Physics, University of California San Diego, 
La Jolla, CA 92093
3 Center for Theoretical Biological Physics and Department of 
Bioengineering, Rice University, Houston, TX 77251


PNAS, in press

Natural chemical gradients to which cells respond chemotactically 
are often dynamic, with both spatial and temporal components. A 
primary example is the social amoeba Dictyostelium, which migrates 
to the source of traveling waves of chemoattractant as part of a self-
organized aggregation process. Despite its physiological importance,
 little is known about how cells migrate directionally in response to 
traveling waves.  The classic back-of-the-wave problem is how cells 
chemotax towards the wave source, even though the spatial gradient 
reverses direction in the back of the wave.  Here we address this 
problem by using microfluidics to expose cells to traveling waves of 
chemoattractant with varying periods. We find that cells exhibit 
cellular memory and maintain directed motion towards the wave 
source in the back of the wave for the natural period of 6 minutes, 
but increasingly reverse direction for longer wave periods. Further 
insights into cellular memory are provided by experiments quantifying 
cell motion and localization of a directional-sensing marker  after 
rapid gradient switches. The results can be explained by a model that 
couples adaptive directional sensing to bistable cellular memory. Our 
study shows how spatiotemporal cues can guide cell migration over 
large distances.


Submitted by Wouter-Jan Rappel [[log in to unmask]]
==============================================================
[End dictyNews, volume 40, number 23]

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