dictyNews
Electronic Edition
Volume 42, number 27
November 18, 2016
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Abstracts
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Using the social amoeba Dictyostelium to study the functions of
proteins linked to neuronal ceroid lipofuscinosis
Robert J. Huber
Department of Biology, Trent University, Peterborough, Ontario,
Canada
Journal of Biomedical Science, in press
Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease,
is a debilitating neurological disorder that affects both children and
adults. Thirteen genetically distinct genes have been identified that
when mutated, result in abnormal lysosomal function and an
excessive accumulation of ceroid lipofuscin in neurons, as well as
other cell types outside of the central nervous system. The NCL
family of proteins is comprised of lysosomal enzymes (PPT1/CLN1,
TPP1/CLN2, CTSD/CLN10, CTSF/CLN13), proteins that peripherally
associate with membranes (DNAJC5/CLN4, KCTD7/CLN14), a
soluble lysosomal protein (CLN5), a protein present in the secretory
pathway (PGRN/CLN11), and several proteins that display different
subcellular localizations (CLN3, CLN6, MFSD8/CLN7, CLN8,
ATP13A2/CLN12). Unfortunately, the precise functions of many of
the NCL proteins are still unclear, which has made targeted therapy
development challenging. The social amoeba Dictyostelium
discoideum has emerged as an excellent model system for studying
the normal functions of proteins linked to human neurological
disorders. Intriguingly, the genome of this eukaryotic soil microbe
encodes homologs of 11 of the 13 known genes linked to NCL.
The genetic tractability of the organism, combined with its unique
life cycle, makes Dictyostelium an attractive model system for
studying the functions of NCL proteins. Moreover, the ability of human
NCL proteins to rescue gene-deficiency phenotypes in Dictyostelium
suggests that the biological pathways regulating NCL protein function
are likely conserved from Dictyostelium to human. In this review, I will
discuss each of the NCL homologs in Dictyostelium in turn and
describe how future studies can exploit the advantages of the system
by testing new hypotheses that may ultimately lead to effective therapy
options for this devastating and currently untreatable neurological
disorder.
submitted by: Robert Huber [[log in to unmask]]
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A plasma membrane template for macropinocytic cups
Douwe M. Veltman, Thomas D. Williams, Gareth Bloomfield, Bi-Chang
Chen, Eric Betzig, Robert H. Insall & Robert R. Kay
Elife, accepted
Macropinocytosis is a fundamental mechanism that allows cells to take
up extracellular liquid into large vesicles. It critically depends on the
formation of a ring of protrusive actin beneath the plasma membrane,
which develops into the macropinocytic cup. We show that
macropinocytic cups in Dictyostelium are organised around coincident
intense patches of PIP3, active Ras and active Rac. These signalling
patches are invariably associated with a ring of active SCAR/WAVE at
their periphery, as are all examined structures based on PIP3 patches,
including phagocytic cups and basal waves. Patch formation does not
depend on the enclosing F-actin ring, and patches become enlarged
when the RasGAP NF1 is mutated, showing that Ras plays an
instructive role. New macropinocytic cups predominantly form by splitting
from existing ones. We propose that cup-shaped plasma membrane
structures form from self-organizing patches of active Ras/PIP3, which
recruit a ring of actin nucleators to their periphery.
submitted by: Douwe Veltman [[log in to unmask]]
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A core phylogeny of Dictyostelia inferred from genomes representative
of the eight major and minor taxonomic divisions of the group.
Reema Singh, Christina Schilde and Pauline Schaap
School of Life Sciences, University of Dundee, MSI complex, Dow Street,
Dundee DD15EH, UK
BMC Evolutionary Biology, in press
Background: Dictyostelia are a well-studied group of organisms with
colonial multicellularity, which are members of the mostly unicellular
Amoebozoa. A phylogeny based on SSU rDNA data subdivided all
Dictyostelia into four major groups, but left the position of the root and
of 6 group-intermediate taxa unresolved. Recent phylogenies inferred
from 30 or 213 proteins from sequenced genomes, positioned the root
between two branches, each containing two major groups, but lacked
data to position the group-intermediate taxa. Since the positions of these
early diverging taxa are crucial for understanding the evolution of
phenotypic complexity in Dictyostelia, we sequenced six representative
genomes of early diverging taxa.
Results: We retrieved orthologs of 47 housekeeping proteins with an
average size of 890 amino acids from six newly sequenced and eight
published genomes of Dictyostelia and unicellular Amoebozoa and
inferred phylogenies from single and concatenated protein sequence
alignments. Concatenated alignments of all 47 proteins, and 4 out of 5
subsets of 9 concatenated proteins all produced the same consensus
phylogeny with 100% statistical support. Trees inferred from just 2 out
of the 47 proteins, individually, reproduced the consensus phylogeny,
highlighting that single gene phylogenies will rarely reflect correct
species relationships. However, sets of two or three concatenated
proteins again reproduced the consensus phylogeny, indicating that
a small selection of genes suffices for low cost classification of as
yet unincorporated or newly discovered dictyostelid and
amoebozoan taxa by gene amplification.
Conclusions: The multi-locus consensus phylogeny shows that groups
1 and 2 are sister clades in branch I, with the group-intermediate taxon
D. polycarpum positioned as outgroup to group 2. Branch II consists of
groups 3 and 4, with the group-intermediate taxon Polysphondylium
violaceum positioned as sister to group 4, and the group-intermediate
taxon Dictyostelium polycephalum branching at the base of that whole
clade. Given the data, the approximately unbiased test rejects all
alternative topologies favoured by SSU rDNA and individual proteins
with high statistical support. The test also rejects monophyletic origins
for the genera Acytostelium, Polysphondylium and Dictyostelium. The
current position of Acytostelium ellipticum in the consensus phylogeny i
ndicates that somatic cells were lost twice in Dictyostelia.
submitted by: Pauline Schaap [[log in to unmask]]
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[End dictyNews, volume 42, number 27]
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