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Published 31 March 2003. doi:10.1083/jcb.200211091
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© The Rockefeller University Press, 0021-9525/2003/3/1009 $5.00
The Journal of Cell Biology, Volume 160, Number 7, 1009-1015

Report

 uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion

Lars H. Engelholm1,4, Karin List1,4, Sarah Netzel-Arnett2, Edna Cukierman3, David J. Mitola1, Hannah Aaronson1, Lars Kjøller4, Jørgen K. Larsen4, Kenneth M. Yamada3, Dudley K. Strickland5, Kenn Holmbeck2, Keld Danø4, Henning Birkedal-Hansen2, Niels Behrendt4 and Thomas H. Bugge1

1 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
2 Matrix Metalloproteinase Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
3 Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
4 Finsen Laboratory, DK-2100, Copenhagen, Denmark
5 Department of Vascular Biology, American Red Cross, Rockville, MD 20855

Address correspondence to Thomas H. Bugge, Proteases and Tissue Remodeling Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 211, Bethesda, MD 20892. Tel.: (301) 435-1840. Fax: (301) 402-0823. E-mail: thomas.bugge{at}nih.gov

The uptake and lysosomal degradation of collagen by fibroblasts constitute a major pathway in the turnover of connective tissue. However, the molecular mechanisms governing this pathway are poorly understood. Here, we show that the urokinase plasminogen activator receptor–associated protein (uPARAP)/Endo180, a novel mesenchymally expressed member of the macrophage mannose receptor family of endocytic receptors, is a key player in this process. Fibroblasts from mice with a targeted deletion in the uPARAP/Endo180 gene displayed a near to complete abrogation of collagen endocytosis. Furthermore, these cells had diminished initial adhesion to a range of different collagens, as well as impaired migration on fibrillar collagen. These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions.

Key Words: cell adhesion; integrin; matrix internalization; matrix metalloproteinase; uPAR

The online version of this article includes supplemental material.

* Abbreviations used in this paper: FN-II, fibronectin type II; MMP, matrix metalloproteinase; uPARAP, urokinase plasminogen activator receptor–associated protein.


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