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Control of actin dynamics in Dictyostelium
Over the years, the study of the social amoeba D. discoideum has given great
insights into mammalian biochemical systems and mammalian disease
mechanisms. Its similarities to higher eukaryotic systems make it an ideal
organism to study for processes such as actin dynamics, and analysis of the
near-complete genomic sequence has made such similarities even more
apparent (Glockner et al., 2002).
The ease with which Dictyostelium genes can be manipulated has led to its
becoming a powerful tool for the study of cell motility. Numerous mutants
with gene disruptions have been generated, providing a mass of information
about the functions of the pathways leading to actin polymerization and cell
locomotion. For instance, Dictyostelium mutants lacking both isoforms of
profilin have greatly decreased motility, increased F-actin concentration,
impaired cytokinesis and developmental defects, highlighting the role of
profilin as an actin sequestering protein in vivo (Haugwitz et al., 1994).
Capping protein is another important factor in actin polymerization and
functions by terminating growth of actin filament ends. The phenotype of
mutants with decreased levels of capping protein, including increased F-actin
content and slow movement, helped to prove the function of this protein,
previously suggested only in vitro, in living cells (Hug et al., 1995).
Interfering with upstream signalling events has also proved useful in
generating information about the molecular organization of signalling
pathways. The Dictyostelium genome encodes a surprisingly large number
of small GTPases, including at least 13 Rac subfamily members, all
homologous to mammalian Rac1 (Wilkins and Insall, 2001). One study has
outlined the consequences of overactive Rac1B and the absence of Rac1 GAP
(Chung et al., 2000). Both mutants have similar phenotypes, including
ine cient chemotaxis, high number of lateral pseudopods and low cell speed.
This shows that the Rac subfamily of proteins is involved in the regulation of
cell movement through the actin cytoskeleton in Dictyostelium as in mammals.
Another study disrupted the DGAP1 gene, the protein product of which
connects Rac signalling to the actin cytoskeleton, and discovered such
mutants also had increased F-actin contents and large leading edges (Faix et
al., 1998).
The majority of known proteins involved in mammalian actin dynamics
have also been identified in Dictyostelium, allowing cell movement to be
meaningfully researched at a lower rung on the evolutionary ladder. The
major players of the actin nucleating machinery of the cell, including all seven
members of the Arp2/3 complex (Insall et al., 2001), WASp and Scar, are all
present in Dictyostelium and are highly homologous to their mammalian
counterparts. However, it is clear that there are differences; for example,
Cdc42 activity has yet to be demonstrated in Dictyostelium (Wilkins and
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