JBC DNA damage antibodies

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meilinger, M.
Right arrow Articles by Huettinger, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meilinger, M.
Right arrow Articles by Huettinger, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 53, 38091-38096, December 31, 1999

Metabolism of Activated Complement Component C3 Is Mediated by the Low Density Lipoprotein Receptor-related Protein/alpha 2-Macroglobulin Receptor*

Melinda Meilinger, Christa Gschwentner, Irmgard Burger, Markus Haumer, Markus Wahrmann, Lajos SzollarDagger , Johannes Nimpf§, and Manfred Huettinger∥

From the Department of Medical Chemistry, University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria, the Dagger  Institute of Pathophysiology, Semmelweis University Medical School, Budapest H-1089, Hungary, and the § Department of Molecular Genetics, University of Vienna, A-1030 Vienna, Austria

Complement component 3 (C3) and alpha 2-macroglobulin evolved from a common, evolutionarily old, ancestor gene. Low density lipoprotein-receptor-related protein/alpha 2-macroglobulin receptor (LRP/alpha 2MR), a member of the low density lipoprotein receptor family, is responsible for the clearance of alpha 2-macroglobulin-protease complexes. In this study, we examined whether C3 has conserved affinity for LRP/alpha 2MR. Ligand blot experiments with human 125I-C3 on endosomal proteins show binding to a 600-kDa protein, indistinguishable from LRP/alpha 2MR by the following criteria: it is competed by receptor-associated protein (the 39-kDa receptor-associated protein that impairs binding of all ligands to LRP/alpha 2MR) and by lactoferrin and Pseudomonas exotoxin, other well known ligands of the multifunctional receptor. Binding of C3 is sensitive to reduction of the receptor and is Ca2+-dependent. All these features are typical for cysteine-rich binding repeats of the low density lipoprotein receptor family. In LRP/alpha 2MR, they are found in four cassettes (2, 8, 10, and 11 repeats). Ligand blotting to chicken LR8 demonstrates that a single 8-fold repeat is sufficient for binding. Confocal microscopy visualizes initial surface labeling of human fibroblasts incubated with fluorescent labeled C3, which changes after 5 min to an intracellular vesicular staining pattern that is abolished in the presence of receptor-associated protein. Cell uptake is abolished in mouse fibroblasts deficient in LRP/alpha 2MR. Native plasma C3 is not internalized. We demonstrate that the capacity to internalize C3 is saturable and exhibits a KD value of 17 nM. After intravenous injection, rat hepatocytes accumulate C3 in sedimentable vesicles with a density typical for endosomes. In conclusion, our ligand blot and uptake studies demonstrate the competence of the LRP/alpha 2MR to bind and endocytose C3 and provide evidence for an LRP/alpha 2MR-mediated system participating in C3 metabolism.

* This work was supported by Boehringer Ingelheim and the European Community BIOMED2 Grant BMH4-CT96-0162.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by Austrian Science Foundation Grant F-0606.

∥ To whom correspondence should be addressed. Tel.: 43-1-4277-60821; Fax: 43-1-4277-60881; E-mail: manfred.huetttinger@univie.ac.at.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
A. Gaultier, S. Arandjelovic, S. Niessen, C. D. Overton, M. F. Linton, S. Fazio, W. M. Campana, B. F. Cravatt III, and S. L. Gonias
Regulation of tumor necrosis factor receptor-1 and the IKK-NF-{kappa}B pathway by LDL receptor-related protein explains the antiinflammatory activity of this receptor
Blood, June 1, 2008; 111(11): 5316 - 5325.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
Mahnke, Guo, Lee, Sepulveda, S. Swain, Nussenzweig, and R. Steinman
The Dendritic Cell Receptor for Endocytosis, DEC-205, Can Recycle and Enhance Antigen Presentation via Major Histocompatibility Complex Class II-positive Lysosomal Compartments
J. Cell Biol., October 30, 2000; 151(3): 673 - 684.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Westein, C. V. Denis, B. N. Bouma, and P. J. Lenting
The alpha -Chains of C4b-binding Protein Mediate Complex Formation with Low Density Lipoprotein Receptor-related Protein
J. Biol. Chem., January 18, 2002; 277(4): 2511 - 2516.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.