Biology Reference
In-Depth Information
Mechanistic insights into E-cadherin function during cell-cell
adhesion
Cell-cell contact has been proposed to act as a trap for cadherin that is freely
diffusing within the plasma membrane, as originally envisioned in the
diffusion-trap model (Singer, 1976; McCloskey and Poo, 1986). In this
model, E-cadherin at the contact site rapidly becomes immobile. Results with
live cell imaging analysis strongly supports this model. Several roles for
cadherin in this process can be considered. Trans interactions between
adjacent cells could provide the initial mechanism for a diffusion trapping
system. Cis interactions of cadherins, between cadherin molecules on the same
cell, could provide a secondary mechanism to recruit and retain cadherins at
contact sites. Besides these structural roles, signalling pathways initiated by
cadherin engagement in trans could result in further accumulation of
immobile cadherins at contact sites. Activation of Rho GTPases (discussed
below) could direct changes in actin organization that provide additional
binding sites for freely diffusive cadherins at cell-cell contacts. Diffusion and
trapping of E-cadherin at the contact would increase the local concentration
of cadherin, thereby resulting in strengthening of cell-cell adhesion. Thus,
short-range diffusion trapping around immobilized E-cadherin may be
important for clustering E-cadherin within the cell-cell contact.
The role of Rho family small GTPases and membrane
dynamics in cell-cell adhesion
Our time-lapse imaging of live MDCK epithelial cells expressing a GFP fusion
to E-cadherin demonstrates that contact between migratory cells is an
opportunistic event to which migratory cells must respond rapidly in order to
convert a transient contact into strong adhesion (Adams et al., 1998). This
description of adhesion dynamics has led us to inquire about the interplay
between the cellular machinery involved in cell migration, the initiation of
cell-cell adhesion, and the subsequent
suppression of
the migratory
phenotype.
The Rho family of small GTPases has been shown to play an important role
in cell migration and plasma membrane dynamics, and a role for these
proteins in cell-cell adhesion has long been sought (Bishop and Hall, 2000).
Prior studies from our laboratory indicate that lamellipodia extension, a
Rac1-driven process (Nobes and Hall, 1995), is important in enlarging
cell-cell contacts (McNeill et al., 1990) as shown also in keratinocytes (Braga
et al., 1997, 1999). Recent reports demonstrate increased activity levels of
