HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 7, 4165-4176, February 15, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/7/4165    most recent M708723200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wood, R. J. Articles by Hulett, M. D. Search for Related Content PubMed PubMed Citation Articles by Wood, R. J. Articles by Hulett, M. D. Social Bookmarking                      What's this?

Cell Surface-expressed Cation-independent Mannose 6-Phosphate Receptor (CD222) Binds Enzymatically Active Heparanase Independently of Mannose 6-Phosphate to Promote Extracellular Matrix Degradation^*

From the Cancer and Molecular Immunology Group, Division of Molecular Bioscience, The John Curtin School of Medical Research, The Australian National University, Acton, Australian Capital Territory 2601, Australia

Heparanase is a β-D-endoglucuronidase that cleaves heparan sulfate, an important structural component of the extracellular matrix (ECM) and vascular basement membrane (BM). The cleavage of heparan sulfate by heparanase-expressing cells, such as activated leukocytes, metastatic tumor cells, and proliferating endothelial cells, facilitates degradation of the ECM/BM to promote cell invasion associated with inflammation, tumor metastasis, and angiogenesis. In addition to its enzymatic function, heparanase has also recently been shown to act as a cell adhesion and/or signaling molecule upon interaction with cell surfaces. Despite the obvious importance of the mechanisms for the binding of heparanase to cell surfaces, the receptor(s) for heparanase remain poorly defined. In this study, we identify the 300-kDa cation-independent mannose 6-phosphate receptor (CIMPR) as a cell surface receptor for heparanase. Purified platelet heparanase was shown to bind the human CIMPR expressed on the surface of a transfected mouse L cell line. Optimal binding was determined to be at a slightly acidic pH (6.5-7.0) with heparanase remaining on the cell surface for up to 10 min at 37 °C. In contrast, mouse L cells or Chinese hamster ovary cells expressing the cation-dependent mannose 6-phosphate receptor (CDMPR) showed no binding of heparanase. Interestingly, the binding of heparanase to CIMPR was independent of Man-6-P moieties. Significantly, primary human T cells upon activation were shown to dramatically up-regulate levels of cell surface-expressed CIMPR, which showed a concomitant increase in their capacity to bind heparanase. Furthermore, the tethering of heparanase to the surface of cells via CIMPR was found to increase their capacity to degrade an ECM or a reconstituted BM. These data suggest an important role for CIMPR in the cell surface presentation of enzymatically active heparanase for the efficient passage of T cells into an inflammatory site and have implications for the use of this mechanism by other cell types to enhance cell invasion.

Received for publication, October 22, 2007

^* This work was supported in part by a Program Grant from the National Health and Medical Research Council of Australia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Recipient of an Australian postgraduate awards scheme.

² To whom correspondence should be addressed. Tel.: 61-261254480; Fax: 61-261252499; E-mail: mark.hulett{at}anu.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Fux, N. Feibish, V. Cohen-Kaplan, S. Gingis-Velitski, S. Feld, C. Geffen, I. Vlodavsky, and N. Ilan Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling Cancer Res., March 1, 2009; 69(5): 1758 - 1767. [Abstract] [Full Text] [PDF]

				P. Sun, D. E. Sleat, M. Lecocq, A. R. Hayman, M. Jadot, and P. Lobel Acid phosphatase 5 is responsible for removing the mannose 6-phosphate recognition marker from lysosomal proteins PNAS, October 28, 2008; 105(43): 16590 - 16595. [Abstract] [Full Text] [PDF]

				N. M Dahms, L. J Olson, and J.-J. P Kim Strategies for carbohydrate recognition by the mannose 6-phosphate receptors Glycobiology, September 1, 2008; 18(9): 664 - 678. [Abstract] [Full Text] [PDF]