dictyNews
Electronic Edition
Volume 43, number 8
April 21, 2017
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Abstracts
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Mroh1, a lysosomal regulator localised by WASH-generated actin
Peter A. Thomason, Jason S. King* and Robert H. Insall
Address: Cancer Research UK Beatson Institute, Garscube Estate,
Switchback Road, Glasgow, G61 1BD, United Kingdom
*Present Address: School of Biomedical Sciences, University of
Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN,
United Kingdom
Journal of Cell Science, in press
The steps leading to constitutive exocytosis are poorly understood.
In Dictyostelium WASH complex mutants, exocytosis is blocked, so
cells that take up fluorescent dextran from the medium retain it and
remain fluorescent. Here we establish a FACS-based method to select
cells that retain fluorescent dextran, allowing identification of mutants
with disrupted exocytosis. Screening a pool of random mutants
identified the WASH complex, as expected, and multiple mutants in the
conserved HEAT-repeat containing protein Mroh1. In mroh1 mutants,
endosomes develop normally until the stage where lysosomes
neutralize to postlysosomes, but thereafter the WASH complex is
recycled inefficiently, and subsequent exocytosis is substantially
delayed. Mroh1 protein localizes to lysosomes in mammalian and
Dictyostelium cells. In Dictyostelium it accumulates on lysosomes as
they mature, and is removed together with WASH shortly before the
postlysosomes are exocytosed. WASH-generated F-actin is required
for correct subcellular localisation; in WASH complex mutants, and
immediately after latrunculin treatment, Mroh1 relocalises from
cytoplasm to small vesicles. Thus Mroh1 is involved in a late and
hitherto undefined actin-dependent step in exocytosis.
submitted by: Robert Insall [[log in to unmask]]
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Mycobacterium marinum antagonistically induces an autophagic
response while repressing the autophagic flux in a TORC1- and
ESX-1-dependent manner
Elena Cardenal-Muñoz*, Sonia Arafah, Ana Teresa López-Jiménez,
Sébastien Kicka, Alexandra Falaise, Frauke Bach, Olivier Schaad,
Jason S. King, Monica Hagedorn and Thierry Soldati
*Corresponding author
PLoS Pathogens, in press
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006344
Autophagy is a eukaryotic catabolic process also participating in cell-
autonomous defence. Infected host cells generate double-membrane
autophagosomes that mature in autolysosomes to engulf, kill and digest
cytoplasmic pathogens. However, several bacteria subvert autophagy and
benefit from its machinery and functions. Monitoring infection stages by
genetics, pharmacology and microscopy, we demonstrate that the ESX-1
secretion system of Mycobacterium marinum, a close relative to
M. tuberculosis, upregulates the transcription of autophagy genes, and
stimulates autophagosome formation and recruitment to the mycobacteria-
containing vacuole (MCV) in the host model organism Dictyostelium.
Antagonistically, ESX-1 is also essential to block the autophagic flux and
deplete the MCV of proteolytic activity. Activators of the TORC1 complex
localize to the MCV in an ESX-1-dependent manner, suggesting an
important role in the manipulation of autophagy by mycobacteria. Our
findings suggest that the infection by M. marinum activates an autophagic
response that is simultaneously repressed and exploited by the bacterium
to support its survival inside the MCV.
submitted by: Thierry Soldati [log in to unmask]]
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[End dictyNews, volume 43, number 8]
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