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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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