Biology Reference
In-Depth Information
mutants exhibit reduced close contact surface area that results in aberrant
motility, are highly defective in the internalization of a variety of particle types
(i.e., latex beads, yeast, bacteria) and do not exhibit Ca
2+
-dependent cell-cell
adhesion during early aggregation (Niewo¨ hner et al., 1997; Tuxworth et al.,
2001). These observations suggest that TalA and DdM7 may interact with
each other and preliminary co-immunoprecipitation experiments indicate that
they do (Tuxworth, Stephens and Titus, unpublished).
It is interesting to note that both TalA and DdM7 have FERM domains
(Figure 2.1), suggesting that their shared interaction or function may be
dictated by the presence of this domain. Furthermore, a number of FERM
domain proteins play a role in cell-substrate adhesion. Members of the ERM
(ezrin, radixin, moesin) family of actin binding proteins are required for both
the extension of actin-based structures such as microvilli, as well as for
adhesion to surfaces (Takeuchi et al., 1994; Paglini et al., 1998; Bonilha et al.,
1999; Yonemura and Tsukita, 1999). Major components of the focal contact,
such as FAK (focal adhesion kinase) possess a FERM domain (Schaller et al.,
1995). In the case of mammalian cells, direct links between FERM proteins
and adhesion receptors have been established. The best example of this is the
direct binding of the talin FERM domain to b integrin or the binding of the
Na
+
/H
+
exchanger NHE1 to ezrin (Calderwood et al., 1999; Denker et al.,
2000). Additionally, a PDZ protein, EBP50, has been shown to bind to the
FERM domain of ezrin and moesin, likely mediating the interaction of these
proteins with the renal brush border Na
+
/H
+
exchanger (Reczek et al., 1997).
One possibility is either that TalA and DdM7 bind to the same integral
membrane receptor or transmembrane linker protein, providing a connection
to DdCAD-1 and organizing the receptor(s) into a high avidity complex.
Binding of just one of these proteins would be insucient for promoting
substrate binding. Alternatively, an adaptor protein, similar to EBP50, might
first bind to both DdM7 and TalA and then this complex would bind to and
organize receptors in the plane of the membrane.
An alternative explanation for the observed similarity of the DdM7 and
talA null mutant phenotypes is that TalA serves as a DdM7 receptor. This
seems unlikely as the distribution of TalA appears to be broader than that of
M7 (Kreitmeier et al., 1995; Tuxworth et al., 2001; Hibi et al., 2003). While it
is enriched at the leading edge of a chemotactic cell it is also found all around
the periphery of the cell. Also, it is along the length of the filopodia in addition
to being localized to the tip. This contrasts with that of M7, which is only
found in dynamic regions of the cell, i.e., those areas of the cell undergoing
extension, and appears to be largely at the tips of filopodia. Furthermore,
while the phenotypes of the two null mutants are quite similar there are some
notable differences. The talA mutant extends filopodia while the DdM7 null
does not, the phagocytic defect of the talA mutant can be rescued partially by
adhesive bacteria while the DdM7 null mutant phenotype can not (Niewo¨ hner
