Biology Reference
In-Depth Information
organized actin-based structures. DdM7 is restricted to the tips of filopodia,
the leading edge of chemotactic cells and the phagocytic cup (Tuxworth et al.,
2001). Its localization is dynamic. For example, DdM7 is associated with the
growing phagocytic cup, but once it is almost fully formed, DdM7 disappears.
The DdM7 null mutant has a pronounced adhesion defect (Tuxworth et al.,
2001). These cells no longer make broad regions of close contact with the
substratum and instead only the rear of the cell maintains a contact with a
small surface area. The DdM7 null cells are capable of making pseudopodia
but these often protrude off the surface and do not touch down for significant
periods of time. These null cells also do not make filopodia. The DdM7 nulls
bind particles more poorly and, as one would expect, have a significant
phagocytosis defect regardless of the particle type (Titus, 1999; Tuxworth et
al., 2001). Aggregation-stage cells also exhibit a defect in Ca
2+
-dependent
cell-cell adhesion; however, the cells are capable of aggregating, undergoing
morphogenesis and completing the developmental cycle. Analysis of two
known adhesion receptors, Phg1 and gp130, in the DdM7 null mutant as well
as localization studies indicates that this motor protein is not acting as a
transport motor to supply adhesion receptors to the cell surface. The available
data suggest instead that DdM7 acts at the plasma membrane to promote the
binding of the cell to surfaces, possibly by cooperating in the formation of a
high avidity complex of receptors linked to the underlying actin cytoskeleton
(Tuxworth et al., 2001).
It is informative to compare the DdM7 null mutant phenotype with that of
the sh1 mutant mouse. In both mutants, the observed phenotype is consistent
with defects in adhesion. The DdM7 mutant does not bind a wide range of
surfaces while the defect in the sh1 mice is apparently highly specific - the link
between neighbouring cochlear hair cell SC is not formed, resulting in a
disordered and non-functional hair bundle. The SC-SC links are calcium-
dependent and formed by cadherins andM7a is linked to one of these, cadherin-
23, through an adaptor protein, harmonin. Aggregating DdM7 null mutant do
not have Ca
2+
-dependent cell-cell adhesion. This cell-cell interaction is
mediated by DdCAD-1, a protein with some similarity to cadherins. The link
between DdM7 and DdCAD-1 is not known at present however it is most
certainly an indirect one, as is the case for M7a and cadherin 23 in mammals.
Taken together, these observations suggest that the general function of M7a has
been throughout evolution and that ongoing studies of DdM7 may provide
additional insight into the function of M7a in higher eukaryotes.
A link between M7 and talin?
Comparison of the available Dictyostelium adhesion mutants reveals a strong
similarity between the DdM7 and talA null mutant phenotypes. These
