Gelsolin is a key player in the regulation of the actin cytoskeleton in life and death. It is regulated by Ca2+ and PIP2 to sever the actin scaffold, and it is activated by caspase cleavage during apoptosis. Overexpression of gelsolin modulates membrane signaling.
Using multiple biophysical approaches, we probed the mechanisms by which Ca2+ and PIP2 regulate gelsolin interaction with actin, and identified several PIP2 binding sites.
We now want to know how gelsolin and gelsolin-like proteins behave in living cells. We are developing a fluorescence energy transfer reporter to monitor gelsolin activation in live cells.