GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis

Sturge, Justin; Wienke, Dirk; East, Lucy; Jones, Gareth E.; Isacke, Clare M.

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.

Citation

Sturge, J., Wienke, D., East, L., Jones, G. E., & Isacke, C. M. (2003). GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis. Journal of Cell Biology, 162(5), 789-794. https://doi.org/10.1083/jcb.200302124

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2003
• Online Publication Date: Sep 2, 2003
• Publication Date: Sep 1, 2003
• Deposit Date: Jun 27, 2019
• Publicly Available Date: Jul 3, 2019
• Journal: Journal of Cell Biology
• Print ISSN: 0021-9525
• Publisher: Rockefeller University Press
• Peer Reviewed: Peer Reviewed
• Volume: 162
• Issue: 5
• Pages: 789-794
• DOI: https://doi.org/10.1083/jcb.200302124
• Keywords: Cdc42; endocytosis; migration; Rac; uPA
• Public URL: https://hull-repository.worktribe.com/output/2005823
• Publisher URL: http://jcb.rupress.org/content/162/5/789
• Contract Date: Jul 3, 2019