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Direct cadherin-activated cell signaling: a view from the plasma membrane.

Yap AS, Kovacs EM - J. Cell Biol. (2002)

Bottom Line: Classical cadherin adhesion molecules are key determinants of cell recognition and tissue morphogenesis, with diverse effects on cell behavior.Recent developments indicate that classical cadherins are adhesion-activated signaling receptors.In particular, early-immediate Rac signaling is emerging as a mechanism to coordinate cadherin-actin integration at the plasma membrane.

View Article: PubMed Central - PubMed

Affiliation: School for Biomedical Science and Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia 4072. a.yap@mailbox.uq.edu.au

ABSTRACT
Classical cadherin adhesion molecules are key determinants of cell recognition and tissue morphogenesis, with diverse effects on cell behavior. Recent developments indicate that classical cadherins are adhesion-activated signaling receptors. In particular, early-immediate Rac signaling is emerging as a mechanism to coordinate cadherin-actin integration at the plasma membrane.

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A model for cadherin-activated Rac signaling participation in early cell–cell recognition. (A) Productive cadherin ligation in newly forming contacts (1) activates Rac signaling at the plasma membrane via a PI3 kinase–dependent intermediary step (2) and possibly also a pathway independent of PI3 kinase (3). One key consequence of Rac activation is the stimulation of cadherin-directed actin assembly by Arp2/3 (4), thereby leading to protrusion of the cell surface (5). (B) Cadherin-directed actin assembly, coordinated by Rac activation, is predicted to direct the surface-protrusive activity of the actin cytoskeleton toward such nascent contacts, to extend the regions of contact and ultimately stabilize cell–cell adhesion.
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fig1: A model for cadherin-activated Rac signaling participation in early cell–cell recognition. (A) Productive cadherin ligation in newly forming contacts (1) activates Rac signaling at the plasma membrane via a PI3 kinase–dependent intermediary step (2) and possibly also a pathway independent of PI3 kinase (3). One key consequence of Rac activation is the stimulation of cadherin-directed actin assembly by Arp2/3 (4), thereby leading to protrusion of the cell surface (5). (B) Cadherin-directed actin assembly, coordinated by Rac activation, is predicted to direct the surface-protrusive activity of the actin cytoskeleton toward such nascent contacts, to extend the regions of contact and ultimately stabilize cell–cell adhesion.

Mentions: Importantly, actin assembly by the Arp2/3 complex is quite strictly activated by cell signals, including Cdc 42 and Rac (Pollard et al., 2000). One function of cadherin-activated Rac signaling may therefore be to stimulate catalytic activity of the Arp2/3 complex when it is recruited to the cell surface by cadherin ligation. Consistent with this notion, both Rac and Arp2/3 localized in newly forming cadherin contacts (Kovacs et al., 2002a,b), whereas inhibition of Rac signaling blocked actin assembly at sites of adhesion between cells and N-cadherin–coated beads (Lambert et al., 2002). As a working model, we therefore propose that the membrane-local activation of Rac plays a key role in early adhesive cell recognition by recruiting and/or activating the actin assembly apparatus in response to E-cadherin ligation (Fig. 1), thereby directing Arp2/3-based surface protrusiveness to efficiently expand zones of cell contact. Later effects of cadherin signaling may further remodel the actin cytoskeleton, for example through regulation of myosin-based contractility by Rho (Charrasse et al., 2002; Vaezi et al., 2002).


Direct cadherin-activated cell signaling: a view from the plasma membrane.

Yap AS, Kovacs EM - J. Cell Biol. (2002)

A model for cadherin-activated Rac signaling participation in early cell–cell recognition. (A) Productive cadherin ligation in newly forming contacts (1) activates Rac signaling at the plasma membrane via a PI3 kinase–dependent intermediary step (2) and possibly also a pathway independent of PI3 kinase (3). One key consequence of Rac activation is the stimulation of cadherin-directed actin assembly by Arp2/3 (4), thereby leading to protrusion of the cell surface (5). (B) Cadherin-directed actin assembly, coordinated by Rac activation, is predicted to direct the surface-protrusive activity of the actin cytoskeleton toward such nascent contacts, to extend the regions of contact and ultimately stabilize cell–cell adhesion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172751&req=5

fig1: A model for cadherin-activated Rac signaling participation in early cell–cell recognition. (A) Productive cadherin ligation in newly forming contacts (1) activates Rac signaling at the plasma membrane via a PI3 kinase–dependent intermediary step (2) and possibly also a pathway independent of PI3 kinase (3). One key consequence of Rac activation is the stimulation of cadherin-directed actin assembly by Arp2/3 (4), thereby leading to protrusion of the cell surface (5). (B) Cadherin-directed actin assembly, coordinated by Rac activation, is predicted to direct the surface-protrusive activity of the actin cytoskeleton toward such nascent contacts, to extend the regions of contact and ultimately stabilize cell–cell adhesion.
Mentions: Importantly, actin assembly by the Arp2/3 complex is quite strictly activated by cell signals, including Cdc 42 and Rac (Pollard et al., 2000). One function of cadherin-activated Rac signaling may therefore be to stimulate catalytic activity of the Arp2/3 complex when it is recruited to the cell surface by cadherin ligation. Consistent with this notion, both Rac and Arp2/3 localized in newly forming cadherin contacts (Kovacs et al., 2002a,b), whereas inhibition of Rac signaling blocked actin assembly at sites of adhesion between cells and N-cadherin–coated beads (Lambert et al., 2002). As a working model, we therefore propose that the membrane-local activation of Rac plays a key role in early adhesive cell recognition by recruiting and/or activating the actin assembly apparatus in response to E-cadherin ligation (Fig. 1), thereby directing Arp2/3-based surface protrusiveness to efficiently expand zones of cell contact. Later effects of cadherin signaling may further remodel the actin cytoskeleton, for example through regulation of myosin-based contractility by Rho (Charrasse et al., 2002; Vaezi et al., 2002).

Bottom Line: Classical cadherin adhesion molecules are key determinants of cell recognition and tissue morphogenesis, with diverse effects on cell behavior.Recent developments indicate that classical cadherins are adhesion-activated signaling receptors.In particular, early-immediate Rac signaling is emerging as a mechanism to coordinate cadherin-actin integration at the plasma membrane.

View Article: PubMed Central - PubMed

Affiliation: School for Biomedical Science and Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Australia 4072. a.yap@mailbox.uq.edu.au

ABSTRACT
Classical cadherin adhesion molecules are key determinants of cell recognition and tissue morphogenesis, with diverse effects on cell behavior. Recent developments indicate that classical cadherins are adhesion-activated signaling receptors. In particular, early-immediate Rac signaling is emerging as a mechanism to coordinate cadherin-actin integration at the plasma membrane.

Show MeSH
Related in: MedlinePlus