Final Report Summary - STRAPACEMI (Spatio-temporal regulation of antigen presentation and cell migration)
In summary, we have used an interdisciplinary approach to unravel the main molecular mechanisms and physical principles involved in the migration of DCs. We found that immature and mature DCs display distinct migratory behaviors: while immature DCs use a random walk-like locomotion mode, mature DCs migrate in a fast and persistent (directional) manner. These differences result from distinct localizations of the actin-based motor protein Myosin II due to the differential use of actin nucleation machineries and regulation of intracellular calcium dynamics. We further described a physical model that accounts for these different migratory behaviors. It is worth noting that some of our findings were completely unexpected, for example the negative role of Arp2/3 and actin nucleation at the cell front for locomotion or the requirement of Myosin II for macropinocytosis and intracellular antigen trafficking. This stresses the importance of studying cell migration in cell types others than the classical cellular models that are commonly used by cell biologists but do not necessarily reflect the tremendous diversity of migratory behaviors. Moreover, a novel and original concept emerged from this work: dendritic cells optimize their locomotion mode based on their functional requirements. Indeed, the intermittent-like migration pattern of immature DCs increases their ability to explore the extracellular space and optimizes their chances to find rare targets, providing a putative explanation for their efficiency as immune sentinels. On the other hand, the fast and persistent migration mode of mature DCs allows their efficient arrival to lymph nodes for rapid T lymphocyte activation.