Membrane Compartmentalization during T Cell Receptor Signalling and Immunological Synapse Formation
The interaction between transmembrane proteins, lipids, and cytoskeletal components provides a framework for the compartmentalization of the cell surface. Intense research has focused on lipid rafts, the cholesterol-enriched membrane microdomains containing many signalling molecules. However, recent advances in cellular and molecular imaging have challenged prevailing models on the role of these membrane microdomains in signal transduction and their biological significance in cell physiology. Using the T lymphocyte as an example, we review here some of the current developments in our understanding of compartmentalization of signalling. T cells are useful to study this issue given the confluence of knowledge about the morphology associated with early signalling, about the kinetics of antigen receptor engagement, and about the resulting events leading to activation of these cells. Specifically, activation of the T cell upon T cell receptor (TCR) engagement with specific peptide: major histocompatibility complex (MHC) molecule complexes on the surface of antigen-presenting cells (APC) results in a coordinated redistribution of some cell surface proteins into a morphological structure known as the immunological synapse (IS) within a timeline encompassing antigen receptor signalling. In the context of these events, we examine the potential interactions between cell surface receptors, protein-protein microclusters, and cytoskeletal networks that support the formation of TCR-dependent signalling units or signalosomes in signalling permissive environments.