Over the past two decades, Rap1 has been recognized world-wide to be an important regulator in a large variety of biological events, including chemotaxis. Despite substantial efforts, the regulation of Rap1 in chemotaxis is still not completely understood. In this thesis, four Rap1 activators, GflB, RasGefL, RasGefQ, and GbpD, have been discovered and characterized in amoeba Dictyostelium discoideum. Our results indicate that chemotactic receptors recruits Rap1 activators, especially GflB, to the sides facing the highest amount of chemical waves called “leading edge”, which then communicates the signal received from receptors to locally assemble the crawling machinery that orients movement toward the source. Although some mechanisms are still not fully unraveled, our findings provide a milestone in the understanding how cells decide on the direction in which they need to migrate towards the extracellular chemical cues. We hope that our work enlightens and encourages new ideas and further investigations on understanding this process.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2016|