Figure 8

Scheme depicting BMP2-induced PI3K signalling via p55γ/p110α and cortical actin rearrangements via PIP3-LL5β filamins in mesenchymal progenitor cells. Gradients of BMP2 activate the BMP receptor complex and facilitate the association of BMPRII to regulatory subunit p55γ coupled to class Ia catalytic subunit p110α. The recruitment and activation of PI3K generates the membrane-bound second messenger PIP3 at the leading edge of cells that are about to establish PCP. PIP3 recruits the PH-domain protein LL5β. LL5β co-recruits and tethers the actin crosslinker filamin to the leading edge, where it promotes actin polymerisation, crosslinking and subsequent initiation of lamellipodia formation, extension and protrusion. BMP2, bone morphogenetic protein 2; BMPRI/II, bone morphogenetic protein receptor type I/II; pSmad1, phospho-Smad1; p55γ, PI3K regulatory subunit p55 gamma; p110α, p110 catalytic subunit p110 alpha; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-triphosphate; LL5β, pleckstrin homology-like domain family B member 2; PH, pleckstrin homology domain; F-actin, filamentous actin.