Figure 9.

Model for the role of P-cadherin in CCM. (a) P-cadherin expression promotes CCM through an increase in the strength and anisotropy of physical forces; it is associated with an increase in intercellular stresses anisotropy and strength that promotes collective cell guidance called plithotaxis. P-cadherin expression also increases traction-force anisotropy (through increasing the Tx/Ty ratio) and strength that pull the cell layer. (b) P-cadherin expression induces polarization because it activates Cdc42 through the GEF β-PIX; this generates biological cues, such as polarization of the cell layer, of cryptic lamellipodia and FAs in the migration direction, polarized membrane protrusion generation and FA dynamics, thereby controlling mechanical force anisotropy and strength.