The role of the cytoskeleton in cell specific differentiation

Research

Macropinocytosis by dendritic cells

Dendritic cells are essential for presentation of foreign antigens to T cells to illicit an immune response. They sample their peripheral tissue environment by engulfing large volumes of the surrounding mileu by macropinocytosis. Macropinosomes form from the aggregation of many actin-driven ruffles. This process is down regulated in mature dendritic cells which migrate to secondary lymphoid organs for antigen presentation to T cells. During the initial encounter with antigen there is a brief burst of enhanced macropinocytosis accompanied by a loss of podosomes-cell substrate adhesive structures that are also actin rich. The main thrust of our research is to understand how these two types of actin structures are regulated. Novel regulators of the actin cytoskeleton will be identified and localised by advanced microscopy techniques. (Collaborative project with Colin Watts)

Fig. A. Dendritic cell labelled for F-actin with phalloidin. Projection of a z-series colour coded for depth. Membrane ruffles associated with macropinosome formation rise up from the surface of the cell (coloured green and blue). Podosomes associated with the base of the cell near the substrate are coloured orange.

Fig D. Dendritic cells are the sentinels of the immune system, residing in peripheral tissues, constantly sampling their environment for invading pathogens. The image shows a 3D reconstruction of DCs in the sub-mucosal layers of the small intestine colour-coded for depth. On the left is the view from the front, on the right the rear view.