dictyNews
Electronic Edition
Volume 37, number 7
September 16, 2011
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Abstracts
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The induction of autophagy by mechanical stress
Jason S. King*, Douwe M. Veltman and Robert H. Insall
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road,
Bearsden, Glasgow. G61 1BD
Autophagy, In Press
The ability to respond and adapt to changes in the physical environment is
a universal and essential cellular property. Here we demonstrate that cells
respond to mechanical compressive stress by rapidly inducing autophagosome
formation. We measure this response in both Dictyostelium and mammalian
cells, indicating that this is an evolutionarily conserved, general response to
mechanical stress. In Dictyostelium, the number of autophagosomes increases
20 fold within 10 minutes of 1kPa pressure being applied and a similar response
is seen in mammalian cells after 30 minutes. We show in both cell types that
autophagy is highly sensitive to changes in mechanical pressure and the
response is graduated, with a half-maximal responses at ~0.2kPa, similar to
other mechano-sensitive responses. We further show that the mechanical
induction of autophagy is TOR-independent and transient, lasting until the cells
adapt to their new environment and recover their shape. The autophagic
response is therefore part of an integrated response to mechanical challenge,
allowing cells to cope with a continuously changing physical environment.
Submitted by: Jason King [[log in to unmask]]
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Dictyostelium discoideum nucleoside diphosphate kinase C plays a negative
regulatory role in phagocytosis, macropinocytosis and exocytosis.
Sarah J. Annesley, Ruzica Bago, Maja Herak Bosnar, Vedrana Filic,
Maja Marinovic, Igor Weber, Anil Mehta and Paul R. Fisher.
PLoS One, accepted
Nucleoside diphosphate kinases (NDPKs) are ubiquitous phosphotransfer
enzymes responsible for producing most of the nucleoside triphosphates
except for ATP. This role is important for the synthesis of nucleic acids and
proteins and the metabolism of sugars and lipids. Apart from this housekeeping
role NDPKs have been shown to have many regulatory functions in diverse
cellular processes including proliferation and endocytosis. Although the protein
has been shown to have a positive regulatory role in clathrin- and dynamin-
mediated micropinocytosis, its roles in macropinocytosis and phagocytosis
have not been studied. The additional non-housekeeping roles of NDPK are
often independent of enzyme activity but dependent on the expression level of
the protein. In this study we altered the expression level of NDPK in the model
eukaryotic organism Dictyostelium discoideum through antisense inhibition and
overexpression. We demonstrate that NDPK levels affect growth, endocytosis
and exocytosis. In particular we find that Dictyostelium NDPK negatively regulates
endocytosis in contrast to the positive regulatory role identified in higher eukaryotes.
This can be explained by the differences in types of endocytosis that have been
studied in the different systems - phagocytosis and macropinocytosis in
Dictyostelium compared with micropinocytosis in mammalian cells. This is the first
report of a role for NDPK in regulating macropinocytosis and phagocytosis, the
former being the major fluid phase uptake mechanism for macrophages, dendritic
cells and other (non dendritic) cells exposed to growth factors.
Submitted by: Paul Fisher [[log in to unmask]]
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[End dictyNews, volume 37, number 7]
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