Dorothy A. Schafer, PhD
Regulation of the dynamics of actin filaments and of membrane during cell migration or normal and cancer cells
Metastasis of tumor cells is a major cause of mortality in cancer patients. A key step during invasion of tumor cells into surrounding host tissue is movement of cells across basement membrane barriers and dispersal throughout adjacent and distant tissues. The actin cytoskeleton provides a primary function during cell migration by generating propulsive forces that move cells along directed paths. The actin cytoskeleton also is implicated in maintaining membrane homeostasis, but the biochemical pathways are less clear. The goal of the Schafer lab studies is to understand the mechanisms by which dynamics of actin filaments and of membranes are coordinated during cell migration and for maintaining membrane homeostasis in healthy and tumorous cells. A primary focus of our research is on the GTPase dynamin, a key regulator of membrane trafficking at the plasma membrane. Dynamin also interacts with several important actin binding/regulatory proteins, making it an ideal candidate to coordinate the dynamics of actin filaments and membranes. Dynamin GTPase activity regulates the dynamics of actin filaments at a variety of cellular membranes. Their primary goal is to understand how dynamin and actin filaments function together during cell migration and membrane trafficking.
Their work to understanding the mechanisms by which actin filaments contribute to cell migration focuses on the Ena/VASP family of proteins. Ena/VASP proteins are involved in several key functions that require spatial regulation of the polymerization and morphology of actin filaments. In spite of the recruitment of Ena/VASP proteins to sites of dynamic actin assembly, their mechanism of action is unknown. They've identified and characterized the ability of Ena/VASP proteins to protect filament barbed ends from barbed end capping proteins while retaining actin subunit addition. They call this Ena/VASP-specific activity "anti-capping". Capping protein is one of several actin regulatory proteins whose level of expression is elevated in metastatic tumor cells. Thus, the delicate balance of actin filament barbed end capping and anti-capping activities may define the metastatic phenotype.