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action of these proteins is distinct but overlapping with that of severing
proteins of the gelsolin/villin family. Phosphoinisotides appear to inhibit the
function of gelsolin family, CapZ family and ADF/cofilin family members
while calcium positively regulates the function of proteins of the gelsolin
family. Phosphorylation but not calcium appears to regulate the activity of
ADF/cofilin proteins (for general review see Cooper and Schafer, 2000).
Although the major proteins involved in the actin dynamics are well
identified, it is not clear how these proteins are involved in the integration of
signals that initiate motility or maintain chemotaxis toward or away from a
stimulus source. Further studies remain to be conducted in order better to
understand the role of the actin dynamics in specialized cells such as
enterocytes. This process may be important for intestinal cell plasticity in
response to extracellular signals or cell damage. We propose that the
epithelial-mesenchymal transition process requires both the recruitment of
apical actin and actin-binding proteins bearing multifunctional properties,
such as villin which, with enrichment at the cell leading edge, provide the
dynamic process necessary for cell propulsion. As a general principle we
suggest that the signalling events leading to actin dynamics are mediated by
proteins which are specific to the cell lineage considered and are therefore
recruited to assure dynamic functions, thus increasing the e ciency of the
cellular response. This adaptative process is necessary for epithelial cells to
make a rapid and e cient response to extracellular signals during
physiological or pathological situations without any de novo protein synthesis.
Conversely, we wonder how a protein whose expression is restricted to a
defined tissue can be integrated into signalling pathways but may play an
active role when expressed in another cellular context? MDCK cells, routinely
used for cell motility and morphogenesis experiments, are able easily to
perform the epithelium-mesenchyme transition by using some components of
the minimal molecular machinery described in the previous section. Addition
of villin to a cell that does not express this multifunctional protein can lead to
an increased turnover of actin monomers in the polymerization/depolymer-
ization cycle of actin that controls the dynamics of cell motility, thus acting as
a potentiator (Figure 15.3).
Perspectives
The role of villin in actin dynamics can be due to its severing and/or capping
property. The severing property of villin has been shown to be regulated by its
phosphorylation state (Zhai et al., 2002). Indeed phosphorylated villin is
known to increase actin severing, in vitro. It would thus be interesting to
analyse the consequence of its phosphorylation status in the regulation of
brush border actin dynamics. Moreover, actin dynamics have been shown to
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