Principal Investigator Frank Gertler
ing the knowledge gained through the study of Ena/VASP proteins in neuronal migration, the Gertler lab has identified domains within Ena/VASP, called EVH1 and EVH2, important for regulating cell motility. EVH1 is important for binding of proteins containing a specific prolinerich motif and EVH2 is the actin-binding domain. Interaction with the EVH1 domain allows for intracellular targeting of Ena/VASP proteins to receptor/signaling complexes. In their search of the proteome for these domains, the Gertler lab has identified new members of the signal network including lammellipodin (Lpd) that localizes to the leading edge of the cell membrane. In collaboration with the Yaffe lab, the Gertler lab demonstrated that a PH domain within Lpd binds to PI(3,4)P2, a phosphoinisotide produced in response to chemotactic stimulation. In addition, overabundance of Lpd increases the velocity of lamellipodia protrusion. The loss-offunction phenotype observed with Lpd is more severe than the loss of any one of the Ena/VASP proteins suggesting that Lpd regulates other effectors of the actin-cytoskeleton in addition to the Ena/VASP pathway.