Fig. 2.

Models of CDR formation based on the phosphoinositide conversion from PI(3,4,5)P₃ to PI(3,4)P₂. (A) Upon stimulation with growth factors, PI3K is activated and produce PI(3,4,5)P₃-rich area on the plasma membrane (blue). SH3YL1 is then recruited to the membrane via its SYLF domain that recognizes PI(3,4,5)P₃. SH3YL1 simultaneously makes complex with a phosphoinositide 5-phosphatase SHIP2, resulting in a formation of PI(3,4)P₂-enriched area (red) by dephosphorylation of PI(3,4,5)P₃. Downstream target of PI(3,4)P₂, such as Tapp1, is thought to be involved in actin polymerization. (B) ARAP1, which contains PH domains that collectively bind to PI(3,4,5)P₃, is recruited to the plasma membrane and it then keeps Arf1/5 in a GDP-bound state (blue). When the phosphoinositide conversion from PI(3,4,5)P3 to PI(3,4)P2 takes place, ARAP1 detaches from the plasma membrane, allowing the activation of Arf1/5 into its GTP-bound form (red).