@article { , title = {GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis}, abstract = {Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in cell guidance and chemotaxis during normal and pathological events. uPAR is GPI-anchored and the mechanism by which it transmits intracellular polarity cues across the plasma membrane during directional sensing has not been elucidated. The constitutively recycling endocytic receptor Endo180 forms a trimolecular complex with uPAR in the presence of uPA, hence its alternate name uPAR-associated protein. Here, we demonstrate that Endo180 is a general promoter of random cell migration and has a more specific function in cell chemotaxis up a uPA gradient. Endo180 expression was demonstrated to enhance uPA-mediated filopodia production and promote rapid activation of Cdc42 and Rac. Expression of a noninternalizing Endo180 mutant revealed that promotion of random cell migration requires receptor endocytosis, whereas the chemotactic response to uPA does not. From these studies, we conclude that Endo180 is a crucial link between uPA-uPAR and setting of the internal cellular compass.}, doi = {10.1083/jcb.200302124}, eissn = {1540-8140}, issn = {0021-9525}, issue = {5}, journal = {Journal of Cell Biology}, pages = {789-794}, publicationstatus = {Published}, publisher = {Rockefeller University Press}, url = {https://hull-repository.worktribe.com/output/2005823}, volume = {162}, keyword = {Cdc42, endocytosis, migration, Rac, uPA}, year = {2003}, author = {Sturge, Justin and Wienke, Dirk and East, Lucy and Jones, Gareth E. and Isacke, Clare M.} }