Building actin structures
TubulinActin
Directed cell migration plays vital roles throughout the course of our lives. During embryonic development, cellular motility of multipotent precursor cells is crucial to the proper patterning and formation of many tissues. When these cells fail to migrate or if their motility is not synchronized with the developmental program, congenital birth defects may arise. Later in life, migration is a fundamental part of tissue remodeling and wound healing. In addition, cellular motility plays essential roles in immune function, for example, during leukocyte recognition and elimination of pathogens. However, undesirable migration events contribute to the etiology of many pathological conditions such as atherosclerosis, chronic inflammation, and tumor metastasis. Thus understanding cellular migration at the molecular level is not only an interesting problem for cell biologists, it is also an area where our understanding may profoundly affect human health.

We are focusing on the question: how do cells build actin-based structures required for motility? Lamellipodia and filopodia are two such protrusive, actin-based structures that use the forces produced by polymerization of actin filaments to push the membrane forward. Lamellipodia are broad, flat sheets often used at the leading edge of motile cells for protrusion. The core structural scaffolding within lamellipodia is a network of short, branched actin filaments that are organized into a “dendritic array”. In contrast, filopodia are finger-like protrusions that exhibit cycles of protrusion and retraction and allow the cell to sample the extracellular environment to search for guidance cues. They are built from long, unbranched actin filaments that are extensive bundled by cross-linking proteins and can exhibit lengths from a few to hundreds of microns in length. Projects in the lab are focused on understanding the molecules and principles underlying the assembly, disassembly, and dynamics of filopodia.