Jonathan Rawson

The cytoskeleton plays a crucial role in the maintenance of cell shape, cell movement, and cellular division.  Our laboratory focuses on a conserved family of proteins, the Diaphanous-related formins (Drfs), that act as molecular switches in signaling to the cytoskeleton.  Because Drfs are crucial to many cellular processes, it is vital that these proteins are tightly regulated.  Normally, Drfs exist in an inactive closed state maintained by an intramolecular inhibitory interaction between the Diaphanous-inhibitory domain (DID) and the Diaphanous-autoregulatory domain (DAD).  In response to external stimuli, Drfs are activated by Rho GTPases, which bind to the GTPase Binding Domain (GBD) and open the protein.  However, recent research suggests that an additional activating signal is necessary. Phosphorylation, a common cellular signaling mechanism in many organisms, may very well be this additional signal. While phosphorylation could help facilitate the activation of Drf proteins, it may also serve to traffic Drfs to a specific cellular location(s).  Within one Drf, mDia2, we have identified eight residues that have a high probability of being phosphorylated.  Using site-directed mutagenesis, we have generated mutations of these residues that chemically mimic a constantly phosphorylated state and a constantly non-phosphorylated state of mDia2.  We have expressed the mDia2 mutants in mouse cells and observed mDia2 localization, cell morphology, and potential changes to the cytoskeleton.  Our results indicate that S272 and T329 may have a role in the overall regulation of Drf proteins in cells.

Faculty Mentor: Brad Wallar

Page last modified July 14, 2009