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Proposed model for Sema3E-induced Arf6 activation. Sema3E binding to Plexin-D1 induces PIP5KIβ activation, which generates PI(4,5)P2 locally. PI(4,5)P2 then binds to the PH domain of an Arf6 GEF, GEP100, resulting in Arf6 activation. Active Arf6 itself recruits and further activates PIP5KIβ, likely resulting in increased Arf6 activity. Sema3E-induced Arf6 activation induces rapid FA disassembly and endothelial cell collapse, thereby inhibiting angiogenesis.
