Biology Reference
In-Depth Information
Figure 11.4 The motility cycle of carcinoma cells in response to EGF. (A) The 5-step cycle
of cell crawling starts with extension of lamellipodia in response to EGF stimulation. Initial
lamellipodium extension occurs off of the substratum and does not require integrin
contacts (Bailly et al., 1998). However, once a lamellipodium contacts the substratum,
integrin engagement can stabilize the lamellipodium to define it as the dominant
lamellipodium. Therefore, the direction of initial extension defines the polarity of the cell
and the direction of subsequent cell locomotion. (B) Two actin polymerization transients
occur after EGF stimulation as defined by the appearance of free barbed ends in vivo (Chan
et al., 1998) (
&
). The early transient peaks by 60 s (Bailly et al., 1999) while the late transient
is co-temporal with (
!
) lamellipodium extension and peaks at about 180 s at room
temperature
The actin-associated EGF receptor is the form of the receptor with high
anity for ligand, and is associated with a number of signalling molecules
including phospholipase C (PLC) (Payrastre et al., 1991). In addition, the
direct linkage of PLC to the EGF receptor may localize its initial activation to
the high-anity population of receptors which are believed to signal to
downstream pathways (Payrastre et al., 1991). The proposal (Wells et al.,
1999) that the activation of PLC activity proximal to the EGF receptor causes
hydrolysis of PIP
2
and release of cofilin and gelsolin to allow local remodelling
of the actin cytoskeleton, is consistent with the identification of a signalling
complex containing F-actin and PLC in association with the receptor
(Payrastre et al., 1991). Therefore, the high-a
nity subpopulation of receptors
may be responsible for generating the signal that causes the early actin
polymerization transient and formation of the F-actin-dependent signalling
complex containing activated PI3K.
EGF receptor-associated actin polymerization is independent of cytosolic
Ca
2+
and therefore unlikely to involve gelsolin activity (Rijken et al., 1995).
