Proteolytic Processing of Drosophila melanogaster FGFs

FGF signalling is of major importance for organisms ranging invertebrates to mammals were it is involved in a broad range of processes throughout the development and adulthood. FGF signalling in Drosophila melanogaster includes three FGF ligands and two FGF receptors. However, Drosophila FGFs are approximately three times the size of vertebrate FGFS, containing additional domains that show no homology to other FGF ligands. Recently it has been discovered that in the case of Bnl these additional C- and Nterminal domains are proteolytically removed releasing a protein of approximate size of a vertebrate FGF. Fur1-mediated cleavage of Bnl is crucial for its activity and therefore essential for tracheal patterning in the embryo. Following up on former findings, this work investigated the role of Fur1-mediated processing for all Bnl-regulated processes in greater depth. The conducted experiments showed that indeed Fur1-mediated processing is essential for all tested processes including the formation of terminal tracheal in the larva and the air sac primordium. Moreover first experiments suggest that Fur1-mediated processing of Bnl is part of the regulatory mechanism for the tracheal remodelling during hypoxia. Further the collected data allowed the conclusion that Fur1 is not only involved in a regulatory process, but is indeed representing the rate-limiting factor for Bnl signalling. It could be demonstrated that all Drosophila FGFs are cleaved thereby removing the large additional domains and releasing proteins of approximately the size of a vertebrate FGF. However, Pyr and Ths are not processed by the Fur1 protease as in silico analysis initially suggested. Taken together, the results of this study suggest that proteolytic processing function as a novel general regulatory mechanism for FGF signalling in Drosophila. Additionally the collected data is offering a possible mechanism for the adaptation of tracheal patterning to the oxygen content of the environment