Profilin plays critical roles regulating the actin cytoskeleton in cells. Present at a 1:1 ratio with monomeric actin, Profilin is considered a highly abundant protein in the cytoplasm, however whether these high concentrations of Profilin are bound to actin, free in the cytoplasm or bound to other proteins is not fully resolved. The bulk of profilin-regulated actin dynamics is understood through two canonical binding sites on Profilin, one for actin monomers and the second for poly-L-proline tracts (found key actin regulating proteins Ena/VASP and Formins). Combined these interactions explain observations about the growth rate and architecture of actin filaments and the critical role of distributing a limited amount of actin monomers between actin nucleation systems. Recent evidence from our lab demonstrates that in addition to its roles in actin regulation, Profilin directly binds to and enhances the growth rate of microtubules in cells and in vitro. Further, specific residues on human Profilin-1 are mutated in patients with amyotrophic lateral sclerosis (ALS) and our work has shown that some of these mutations separate actin and/or microtubule functions. We are currently exploring how ALS-relevant profilin mutations participate in regulating either actin, microtubules, or both polymers in the test tube as well as in neuronal cells.
1) To dissect the role of Profilin as an cellular switch between the actin and microtubule cytoskeletons.
2) To investigate the role of Profilin-microtubule interactions in amyotrophic lateral sclerosis.
The Cytoskeleton & Profilin
Control (MT alone)