Figure 5

Model depicting Robo1 and Robo4 mechanism of action in endothelial cell guidance. Cell A: In resting state, in the absence of ligand (serum or Slit2), Robo1 and Robo4 interact and stay in an inactive conformation. On ligand binding, Vilse, a Cdc42-GAP is recruited to CC2 domain of Robo1 and Robo4 resulting in an increase in intracellular Cdc42-GTP levels. The Cdc42-GTP binds to CRIB domain in IRSp53, which changes conformation of IRSp53 from inactive to active state. The active conformation of IRSp53 allows Mena to interact with the exposed SH3 domain of IRSp53. Cell B: In an activated state, Mena recruits the complex to CC2 domain of Robo4's cytoplasmic tail or directly mediates actin nucleation resulting in filopodia formation and directional migration. This cartoon is a working model and is not conclusive.