dictyNews
Electronic Edition
Volume 42, number 26
November 11, 2016
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Abstracts
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A Diaphanous-related formin links Ras-signaling directly to actin
assembly in macropinocytosis and phagocytosis
Alexander Junemann(a), Vedrana Filić(b), Moritz Winterhoff(a),
Benjamin Nordholz(a), Christof Litschko(a), Helena Schwellenbach(a),
Till Stephan(a), Igor Weber(b), and Jan Faix(a)
a) Institute for Biophysical Chemistry, Hannover Medical School,
Carl-Neuberg-Str. 1, 30625 Hannover, Germany;
b) Division of Molecular Biology, Ruđer Bošković Institute,
Bijenička 54, 10000 Zagreb, Croatia.
PNAS, in press
Phagocytosis and macropinocytosis are Ras-regulated and actin-driven
processes that depend on the dynamic rearrangements of the plasma
membrane that protrudes and internalizes extracellular material by
cup-shaped structures. However, the regulatory mechanisms underlying
actin assembly in large-scale endocytosis remain elusive. Here, we
show that the Diaphanous-related formin G (ForG) from the professional
phagocyte Dictyostelium discoideum localizes to endocytic cups.
Biochemical analyses revealed that ForG is a rather weak nucleator but
efficiently elongates actin filaments in the presence of profilin.
Notably, genetic inactivation of ForG is associated with a strongly
impaired endocytosis and a markedly diminished F-actin content at the
base of the cups. By contrast, ablation of the Arp2/3 (actin-related
protein-2/3) complex activator SCAR (suppressor of cAMP receptor)
diminishes F-actin mainly at the cup rim, being consistent with its
known localization. These data therefore suggest that ForG acts as an
actin polymerase of Arp2/3-nucleated filaments to allow for efficient
membrane expansion and engulfment of extracellular material. Finally,
we show that ForG is directly regulated in large-scale endocytosis by
RasB and RasG, which are highly related to the human proto-oncogene
KRas.
submitted by: Jan Faix [[log in to unmask]]
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A set of genes conserved in sequence and expression traces back the
establishment of multicellularity in social amoebae.
Schilde C, Lawal HM, Noegel AA, Eichinger L, Schaap P, Glöckner G
BMC Genomics. 2016 Nov 4;17(1):871
BACKGROUND:
The developmental cycle of Dictyostelid amoebae represents an early
form of multicellularity with cell type differentiation. Mutant
studies in the model Dictyostelium discoideum revealed that its
developmental program integrates the actions of genes involved in
signal transduction, adhesion, motility, autophagy and cell wall and
matrix biosynthesis. However, due to functional redundancy and fail
safe options not required in the laboratory, this single organism
approach cannot capture all essential genes. To understand how
multicellular organisms evolved, it is essential to recognize both
the conserved core features of their developmental programs and the
gene modifications that instigated phenotypic innovation. For complex
organisms, such as animals, this is not within easy reach, but it is
feasible for less complex forms, such as the Dictyostelid social amoebas.
RESULTS:
We compared global profiles of gene expression during the development
of four social amoebae species that represent 600 mya of Dictyostelia
evolution, and identified orthologous conserved genes with similar
developmental up-regulation of expression using three different methods.
For validation, we disrupted five genes of this core set and examined
the phenotypic consequences.
CONCLUSION:
At least 71 of the developmentally regulated genes that were identified
with all methods were likely to be already present in the last ancestor
of all Dictyostelia. The lack of phenotypic changes in null mutants
indicates that even highly conserved genes either participate in
functionally redundant pathways or are necessary for developmental
progression under adverse, non-standard laboratory conditions. Both
mechanisms provide robustness to the developmental program, but impose a
limit on the information that can be obtained from deleting single genes.
submitted by: Gernot Glöckner [[log in to unmask]]
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[End dictyNews, volume 42, number 26]
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