Biology Reference
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(surface-adhesion defective), revealed that the gene encodes an integral
membrane protein with nine transmembrane domains, similar to Phg1, and an
extracellular region that contains three EGF repeats (Fey et al., 2002). In spite
of the gross topological similarity between Phg1 and SadA, these two
molecules are quite distinct from each other. sadA mutants exhibit defects in
phagocytosis and actin organization of growth-phase cells and also have a
cytokinesis defect. Interestingly, the growth phase sadA null cells move at a
faster rate than wild type cells. Aggregation-phase cells do not exhibit
alterations in either adhesion or actin organization and motility is normal.
Consistent with its role in adhesion, SadA is localized around the periphery of
the cell and is not particularly concentrated either in phagocytic cups or at the
leading edge of migrating cells. A number as yet uncharacterized mutants were
obtained in this screen (Fey et al., 2002), as one would expect, and continued
analysis of this collection should provide additional, valuable information
about the means by which Dictyostelium adhere to surfaces, the various
ligands that these cells potentially bind to and how this receptor is associated
with the cytoskeleton.
Links between the Dictyostelium cytoskeleton and adhesion
Studies in mammalian cells have established clearly that integral membrane
receptors are linked to the underlying actin cytoskeleton. Three different
Dictyostelium actin binding proteins, VASP (vasodilator-stimulated phospho-
protein), talinA, DdM7 have been shown to play a role in adhesion during
growth phase and early aggregation. Studies of how these proteins are linked
to extracellular receptors are in their infancy but the available data do provide
some clues and directions for future research.
The Ena/VASP family of proteins regulates actin assembly and plays a role
in cell motility (Bear et al., 2000; Krause et al., 2002). Experiments in
fibroblasts have shown that VASP competes with capping protein for the ends
of actin filaments and cells that do not localize this protein to the leading edge
have shorter, more branched actin filaments in the lamellipodium and move
more rapidly. Conversely, increasing the concentration of VASP in the
lamellipodium results in longer filaments and slower moving cells (Bear et al.,
2002). Dictyostelium has a single VASP gene and GFP-VASP is concentrated
at the leading edge of chemotactic cells, transiently enriched in filopodia and
found at sites of cell-cell contact (Han et al., 2002). VASP null cells exhibit
alterations in actin distribution and extend few, if any filopodia. A
quantitative, three-dimensional analysis of the motility of these null cells
revealed that protrusions extended off the substratum do not make contact
with the surface for unusually long periods of time, suggesting an adhesion
defect. These cells do move slower than controls and tend to move with
