dictyNews
Electronic Edition
Volume 45, number 9
March 15, 2019
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Abstracts
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Dictyostelium: A Model for Studying the Extracellular Vesicle Messengers
Involved in Human Health an Disease
Irène Tatischeff
Honorary CNRS and UPMC Research Director; Founder of RevInterCell
(www.revintercell.com), a Scientific Consulting Service, Orsay, 91400,
France.
Cells, 2019, in press
Special Issue: Simple Organisms for Complex Problems: Modeling
Human Disease in Yeast and Dictyostelium
Cell-derived extracellular vesicles (EVs) are newly uncovered messengers
for intercellular communication. They are released by almost all cell types
in the three kingdoms, Archeabacteria, Bacteria and Eukaryotes. They are
known to mediate important biological functions and to be increasingly
involved in cell physiology and in many human diseases, especially in
oncology. The aim of this review is first to recapitulate the current
knowledge about EVs and to summarize our pioneering work about
Dictyostelium discoideum EVs. However, many challenges remain to be
solved in the EV research field, before any EV application for theranostics
(diagnosis, prognosis and therapy) of human cancers, can be efficiently
implemented in the clinics. Dictyostelium might be an outstanding
eukaryotic cell model for deciphering the utmost challenging problem of
EV heterogeneity, and for unraveling the still mostly unknown mechanisms
of their specific functions as mediators of intercellular communication.
submitted by: Irène Tatischeff [[log in to unmask]]
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Caffeine inhibits PI3K and mTORC2 in Dictyostelium and differentially
affects multiple other cAMP chemoattractant signaling effectors.
A.F.M. Tariqul Islam1, Margarethakay Scavello1, Pouya Lotfi1, Dustin
Daniel1,2, Pearce Haldeman1,3, and Pascale G. Charest1*.
Molecular and Cellular Biochemistry, in press
Caffeine is commonly used in Dictyostelium to inhibit the synthesis of
the chemoattractant cAMP and, therefore, its secretion and the autocrine
stimulation of cells, in order to prevent its interference with the study of
chemoattractant-induced responses. However, the mechanism through
which caffeine inhibits cAMP synthesis in Dictyostelium has not been
characterized. Here, we report the effects of caffeine on the cAMP
chemoattractant signaling network. We found that caffeine inhibits
phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin
complex 2 (mTORC2). Both PI3K and mTORC2 are essential for the
chemoattractant-stimulated cAMP production, thereby providing a
mechanism for the caffeine-mediated inhibition of cAMP synthesis.
Our results also reveal that caffeine treatment of cells leads to an
increase in cAMP-induced RasG and Rap1 activation, and inhibition of
the PKA, cGMP, MyoII, and ERK1 responses. Finally, we observed that
caffeine has opposite effects on F-actin and ERK2 depending on the
assay and Dictyostelium strain used, respectively. Altogether, our findings
reveal that caffeine considerably affects the cAMP-induced chemotactic
signaling pathways in Dictyostelium, most likely acting through multiple
targets that include PI3K and mTORC2.
submitted by: Pascale Charest [[log in to unmask]]
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[End dictyNews, volume 45, number 9]
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