The MRL protein-integrin-talin (MIT) complex forms the molecular basis of sticky fingers that direct cell migration. RIAM and its paralogue, lamellipodin, are the mammalian MRL proteins. (A) The MIT complex, visualized by bimolecular fluorescence complementation (green) between RIAM and integrin αIIbβ3, is enriched at the tips of growing actin filaments (red) in protruding regions of migrating cells. (B) Schematic representation of the MIT complex at the tips of sticky fingers. The N terminus of the MRL protein (RIAM or Lamellipodin) binds talin, thereby enabling its recruitment to the integrin to induce activation. The C terminus of MRL proteins increases processive actin polymerization in part by recruiting ENA/VASP and activators of the ARP2/3 complex to drive the rapid translocation of the integrins. Together, these 2 biochemical functions of the MRL proteins result in the formation of the sticky fingers at the cell edge that direct protrusion during cell migration. Scale bar: 5 μm. Adapted from Lagarrigue et al.¹¹¹