Research

Cytoskeletal signaling through formins

Dynamic rearrangement of the cytoskeleton regulates responses to a variety of extracellular signals that allow cells to move or to change shape. In the past few years substantial progress has been made in understanding some of the principal biochemical reactions and molecules responsible for actin filament growth and structure. These dynamic cytoskeletal rearrangements are controlled by defined signaling pathways, which orchestrate the activity of distinct actin nucleation factors. Only recently do we know that there are over 29 actin nucleators in humans, most of them with unknown physiological and pathophysiological functions, a list that is likely to expand in the near future. The largest family of actin nucleators is represented by the formins, which are characterized by their highly conserved formin homology (FH) domain. Many formins are regulated through physical interactions with Rho family proteins, which can function as molecular switches to relay signal instructions to various cellular responses. Interestingly, many formins govern transcriptional activities through their effects on actin polymerization. One focus of our lab is to understand the synergistic link between formin-induced cytoskeletal dynamics and transcriptional output, which is likely to have substantial implications for cancer cell invasion and metastasis.