Biology Reference
In-Depth Information
the substrate as the rear of the cell retracts. These results point to a critical role
for FAK in the disassembly of adhesions at the rear of the cell as well as at the
front.
A working model
Our observations of adhesion formation, disassembly and turnover in
migrating cells point to the following working model. Integrin ligation to
the ECM initiates the recruitment of signalling and adaptor molecules to
newly forming contact sites. These nascent adhesions, which contain FAK,
paxillin and zyxin, are highly dynamic and in the presence of FAK and Src
activity turn over at the base of the protrusion. The turnover is coupled to the
formation of new protrusions and some components may be reutilized for the
assembly of new adhesions. Although the phosphorylation targets for FAK
and Src in these nascent adhesions are not known, it is interesting to note that
paxillin is a substrate for both of these molecules (Turner, 2000). In the
absence of FAK and Src activity, these developing adhesions grow in size and
molecular complexity as structural molecules, like a-actinin, are recruited to
this site. Once a-actinin is present in the adhesions, they no longer turn over,
but tend to slide inward toward the cell body. Subsequently, visible
concentrations of integrin enter the adhesions and function to stabilize
them. At the cell rear, cleavage of the integrin-cytoskeletal linkage, at a site
proximal to the integrin, initiates breakdown of adhesions. FAK also appears
to be necessary for disassembly of adhesions at the rear of the cell. The
remaining paxillin and a-actinin containing complexes move toward the cell
body and then eventually disperse.
It is presently not known how FAK activity promotes adhesion turnover.
Some possibilities include signalling to activate Rac (or inhibit Rho),
inhibiting contractility, which leads to a loss of organization, and/or post-
translational modifications of a key adaptor molecule resulting in weakened
interactions with other adhesion components. In considering these hypoth-
eses, the generally concerted nature of adhesion turnover points to an event
that rapidly propagates through the adhesion.
Intracellular tracking of adhesion molecules
a5 Integrin resides in vesicles in fibroblasts
In polarized, migrating cells, adhesion components from the front of the cell
accumulate near the cell rear away from the leading edge. It is possible that
mechanisms exist to shuttle these molecules from the cell rear toward the cell
