Protein transduction as a means of effective manipulation of Cdc42 activity in primary T cells.

The Rho family GTPase Cdc42 is a critical regulator of cellular polarization from yeast to man. An analysis of its function in T cell activation is therefore of interest. This analysis poses two substantial challenges, similar to the analysis of many other critical T cell signaling intermediates.

Specific patterns of Cdc42 activity are related to distinct elements of T cell polarization.

T cell polarization toward and within the cellular interface with an APC is critical for effective T cell activation. The Rho family GTPase Cdc42 is a central regulator of cellular polarization. Using live-cell imaging, we characterized the spatiotemporal patterns of Cdc42 activity and their physiological regulation.

Regulation of sustained actin dynamics by the TCR and costimulation as a mechanism of receptor localization.

The localization of receptors, signaling intermediates, and cytoskeletal components at the T cell/APC interface is thought to be a major determinant of efficient T cell activation. However, important questions remain open. What are the dynamics of the T cell cytoskeleton as a potential mediator of such localization? How are they regulated by the TCR and costimulatory receptors? Do they actually mediate receptor localization? In this study, we have addressed these questions.

Interface accumulation of receptor/ligand couples in lymphocyte activation: methods, mechanisms, and significance.

Cellular interaction is vital to the activation of most lymphocytes. At the interface between the lymphocyte and the cell that activates it, multiple receptor/ligand pairs accumulate in distinct patterns. This accumulation is intriguing, as it is likely to shape the quality of receptor signaling and thereby lymphocyte behavior.