Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.

<h4>Background</h4>The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promo...

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Autores principales:	Katia Cortese, Macarena Sahores, Chris D Madsen, Carlo Tacchetti, Francesco Blasi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/402578caa84e4cf390a52002753d71a3
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spelling	oai:doaj.org-article:402578caa84e4cf390a52002753d71a32021-11-25T06:18:31ZClathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.1932-620310.1371/journal.pone.0003730https://doaj.org/article/402578caa84e4cf390a52002753d71a32008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19008962/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1.<h4>Methodology/principal findings</h4>In this study, we have found that along with the ligand-induced down-regulation, uPAR also internalizes and recycles constitutively through a second pathway that is independent of LRP-1 and clathrin but shares some properties with macropinocytosis. The ligand-independent route is amiloride-sensitive, does not require uPAR partitioning into lipid rafts, is independent of the activity of small GTPases RhoA, Rac1 and Cdc42, and does not require PI3K activity. Constitutively endocytosed uPAR is found in EEA1 positive early/recycling endosomes but does not reach lysosomes in the absence of ligands. Electron microscopy analysis reveals the presence of uPAR in ruffling domains at the cell surface, in macropinosome-like vesicles and in endosomal compartments.<h4>Conclusions/significance</h4>These results indicate that, in addition to the ligand-induced endocytosis of uPAR, efficient surface expression and membrane trafficking might also be driven by an uncommon macropinocytic mechanism coupled with rapid recycling to the cell surface.Katia CorteseMacarena SahoresChris D MadsenCarlo TacchettiFrancesco BlasiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 11, p e3730 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katia Cortese Macarena Sahores Chris D Madsen Carlo Tacchetti Francesco Blasi Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
description	<h4>Background</h4>The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1.<h4>Methodology/principal findings</h4>In this study, we have found that along with the ligand-induced down-regulation, uPAR also internalizes and recycles constitutively through a second pathway that is independent of LRP-1 and clathrin but shares some properties with macropinocytosis. The ligand-independent route is amiloride-sensitive, does not require uPAR partitioning into lipid rafts, is independent of the activity of small GTPases RhoA, Rac1 and Cdc42, and does not require PI3K activity. Constitutively endocytosed uPAR is found in EEA1 positive early/recycling endosomes but does not reach lysosomes in the absence of ligands. Electron microscopy analysis reveals the presence of uPAR in ruffling domains at the cell surface, in macropinosome-like vesicles and in endosomal compartments.<h4>Conclusions/significance</h4>These results indicate that, in addition to the ligand-induced endocytosis of uPAR, efficient surface expression and membrane trafficking might also be driven by an uncommon macropinocytic mechanism coupled with rapid recycling to the cell surface.
format	article
author	Katia Cortese Macarena Sahores Chris D Madsen Carlo Tacchetti Francesco Blasi
author_facet	Katia Cortese Macarena Sahores Chris D Madsen Carlo Tacchetti Francesco Blasi
author_sort	Katia Cortese
title	Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
title_short	Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
title_full	Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
title_fullStr	Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
title_full_unstemmed	Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.
title_sort	clathrin and lrp-1-independent constitutive endocytosis and recycling of upar.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/402578caa84e4cf390a52002753d71a3
work_keys_str_mv	AT katiacortese clathrinandlrp1independentconstitutiveendocytosisandrecyclingofupar AT macarenasahores clathrinandlrp1independentconstitutiveendocytosisandrecyclingofupar AT chrisdmadsen clathrinandlrp1independentconstitutiveendocytosisandrecyclingofupar AT carlotacchetti clathrinandlrp1independentconstitutiveendocytosisandrecyclingofupar AT francescoblasi clathrinandlrp1independentconstitutiveendocytosisandrecyclingofupar
_version_	1718413919846924288

Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.

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