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dictyNews Volume 42 Number 08
dictyNews
Electronic Edition
Volume 42, number 8
March 11, 2016
Please submit abstracts of your papers as soon as they have been
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Abstracts
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The inositol-3-phosphate synthase biosynthetic enzyme has
distinct catalytic and metabolic roles
Anna D. Freja, Jonathan Clarkb, Caroline Le Royc, Sergio Lillad,
Peter Thomasond, Grant P. Ottoa, Grant Churchill5, Robert Insalld,
Sandrine P. Clausc, Phillip Hawkinsb, Len Stephensb and
Robin S.B. Williamsa#
Centre for Biomedical Sciences, School of Biological Sciences,
Royal Holloway University of London, Egham, Surrey, UK
a; The Babraham Institute, Cambridge, Cambridgeshire, UK
b; Department of Food and Nutritional Sciences, The University of
Reading, Reading, Berkshire, UK
c. CRUK Beatson Institute for Cancer Research, Glasgow, UK
d. Department of Pharmacology, University of Oxford, Oxford,
Oxfordshire, UK5
Molecular and Cellular Biology, in press
Inositol levels, maintained by the biosynthetic enzyme inositol-3-
phosphate synthase (Ino1), are altered in a range of disorders
including bipolar disorder and Alzheimer’s disease. To date, most
inositol studies have focused on the molecular and cellular effects
of inositol depletion without considering Ino1 levels. Here we
employ a simple eukaryote, Dictyostelium, to demonstrate distinct
effects of loss of Ino1 and inositol depletion. We show that loss
of Ino1 results in inositol auxotrophy that can only be partially
rescued by exogenous inositol. Removal of inositol supplementation
from the ino1- mutant results in a rapid 56% reduction in inositol
levels, triggering the induction of autophagy, reduced cytokinesis
and substrate adhesion. Inositol depletion also caused a dramatic
generalised decrease in phosphoinositide levels that was rescued by
inositol supplementation. However, loss of Ino1 triggered broad
metabolic changes consistent with the induction of a catabolic state
that was not rescued by inositol supplementation. These data suggest
a metabolic role for Ino1 independent of inositol biosynthesis. To
characterise this role, an Ino1 binding partner containing SEL1L1
domains (Q54IX5) was identified with homology to mammalian
macromolecular complex adaptor proteins. Our findings therefore
identify a new role for Ino1, independent of inositol biosynthesis,
with broad effects on cell metabolism.
submitted by: Robin Williams [robin.williams@rhul.ac.uk]
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Non-Catalytic Roles of Presenilin throughout evolution
Grant P. Otto, Devdutt Sharma and Robin S.B. Williams*
Centre for Biomedical Sciences, School of Biological Sciences,
Royal Holloway University of London, Egham, TW20 0EX, UK
Journal of Alzheimer's Disease
Research into Alzheimer’s disease pathology and treatment has
often focused on presenilin proteins. These proteins provide
the key catalytic activity of the gamma-secretase complex in
the cleavage of amyloid precursor protein and resultant amyloid
tangle deposition. Over the last 25 years, screening novel drugs
to control this aberrant proteolytic activity has yet to identify
effective treatments for the disease. In the search for other
mechanisms of presenilin pathology, several studies have
demonstrated that mammalian presenilin proteins also act in a
non-proteolytic role as a scaffold to co-localise key signalling
proteins. This role is likely to represent an ancestral presenilin
function, as it has been described in genetically distant species
including non-mammalian animals, plants and a simple eukaryotic
amoeba Dictyostelium that diverged from the human lineage over a
billion years ago. Here, we review the non-catalytic scaffold role
of presenilin, from mammalian models to other biomedical models,
and include recent insights using Dictyostelium, to suggest that
this role may provide an early evolutionary function of presenilin
proteins.
submitted by: Robin Williams [robin.williams@rhul.ac.uk]
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[End dictyNews, volume 42, number 8]
