Complex cellular processes are governed by signal transduction, which in turn is controlled by protein*protein interactions at the plasma membrane and along the signaling cascade. Biochemical techniques have been used for decades to determine the order of protein interactions along signaling pathways, and the current thrust in cell biology is to understand the role of protein dynamics in signal transduction. For example, a membrane receptor tyrosine kinase is in constant motion as it diffuses on the plasma membrane, interacting with other proteins and membrane microdomains. Ligand binding may lead to a change in diffusive behavior and is often the trigger for receptor homo- or hetero-oligomerization, which initiates receptor phosphorylation and cytoplasmic adaptor protein recruitment. The final step is eventual removal of the activated receptor from the plasma membrane via endocytosis, after which the receptor may be recycled or continue along the endosomal pathway to degradation. Despite this common picture of protein events, there are many details that remain unclear. Recent developments in fluorescence microscopy are allowing us to probe protein behavior in real time, such that we can directly visualize and quantify signal transduction events within the living cell. This seminar will discuss the influence of protein diffusion and membrane structure in protein function, as well as how biophysical techniques, such as single particle tracking, are providing new insights into cell signaling.
