Dr Justin Sturge J.Sturge@hull.ac.uk
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GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis
Sturge, Justin; Wienke, Dirk; East, Lucy; Jones, Gareth E.; Isacke, Clare M.
Authors
Dirk Wienke
Lucy East
Gareth E. Jones
Clare M. Isacke
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 |
Electronic ISSN | 1540-8140 |
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 |
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0
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