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

J. Biol. Chem., Vol. 278, Issue 45, 44799-44807, November 7, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/45/44799    most recent M308982200v1 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 Patel, M. Articles by Tabas, I. Search for Related Content PubMed PubMed Citation Articles by Patel, M. Articles by Tabas, I. Social Bookmarking                      What's this?

The Cytoplasmic Domain of the Low Density Lipoprotein (LDL) Receptor-related Protein, but Not That of the LDL Receptor, Triggers Phagocytosis^*

Mintoo Patel, John Morrow, Frederick R. Maxfield, Dudley K. Strickland¶, Steven Greenberg||, and Ira Tabas**

From the Departments of Medicine, ^||Pharmacology, and ^**Anatomy & Cell Biology, Columbia University, New York, New York 10032, the Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, and the ^¶Department of Vascular Biology, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855

The macrophage LDL receptor and LDL receptor-related protein (LRP, CD91) mediate the phagocytic-like uptake of atherogenic lipoproteins and apoptotic cells, yet the structural basis of their phagocytic functions is not known. To address this issue, we transfected macrophages with chimeric proteins containing the cytoplasmic tails and transmembrane regions of the LDL receptor or LRP and the ectodomain of CD2, which can bind non-opsonized sheep red blood cells (SRBCs). Macrophages expressing receptors containing the LDL receptor domains were able to bind but not internalize SRBCs. In contrast, macrophages expressing receptors containing the cytoplasmic tail of LRP were able to bind and internalize SRBCs. Chimeras in which the LRP cytoplasmic tail was mutated in two di-leucine motifs and a tyrosine in an NPXYXXL motif were able to endocytose anti-CD2 antibody and bind SRBCs, but SRBC phagocytosis was decreased by 70%. Thus, the phagocytic-like functions of LRP, but not those of the LDL receptor, can be explained by the ability of the LRP cytoplasmic tail to trigger phagocytosis. These findings have important implications for atherogenesis and apoptotic cell clearance and for a fundamental cell biological understanding of how the LDL receptor and LRP function in internalization processes.

Received for publication, August 13, 2003

^* This study was supported by Grants HL-57560 (to I. T. and F. R. M.), HL-56984 (to I. T.), HL-54710 (to D. K. S.), and HL-54164 (to S. G.) from the NHLBI, National Institutes of Health. 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.

To whom correspondence should be addressed: Dept. of Medicine, Columbia University, 630 West 168th St., New York, NY 10032. Tel.: 212-305-9430; Fax: 212-305-4834; E-mail: iat1{at}columbia.edu.

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

This article has been cited by other articles:

				A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies Physiol Rev, July 1, 2008; 88(3): 887 - 918. [Abstract] [Full Text] [PDF]

				A. P. Lillis, M. C. Greenlee, I. Mikhailenko, S. V. Pizzo, A. J. Tenner, D. K. Strickland, and S. S. Bohlson Murine Low-Density Lipoprotein Receptor-Related Protein 1 (LRP) Is Required for Phagocytosis of Targets Bearing LRP Ligands but Is Not Required for C1q-Triggered Enhancement of Phagocytosis J. Immunol., July 1, 2008; 181(1): 364 - 373. [Abstract] [Full Text] [PDF]

				S. N. Maiti, K. Balasubramanian, J. A. Ramoth, and A. J. Schroit {beta}-2-Glycoprotein 1-dependent Macrophage Uptake of Apoptotic Cells: BINDING TO LIPOPROTEIN RECEPTOR-RELATED PROTEIN RECEPTOR FAMILY MEMBERS J. Biol. Chem., February 15, 2008; 283(7): 3761 - 3766. [Abstract] [Full Text] [PDF]

				V. Llorente-Cortes, M. Otero-Vinas, S. Camino-Lopez, P. Costales, and L. Badimon Cholesteryl Esters of Aggregated LDL Are Internalized by Selective Uptake in Human Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 117 - 123. [Abstract] [Full Text] [PDF]

				A. J. Merched and L. Chan Absence of p21Waf1/Cip1/Sdi1 Modulates Macrophage Differentiation and Inflammatory Response and Protects Against Atherosclerosis Circulation, December 21, 2004; 110(25): 3830 - 3841. [Abstract] [Full Text] [PDF]

				D. V. Rozanov, E. Hahn-Dantona, D. K. Strickland, and A. Y. Strongin The Low Density Lipoprotein Receptor-related Protein LRP Is Regulated by Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Proteolysis in Malignant Cells J. Biol. Chem., February 6, 2004; 279(6): 4260 - 4268. [Abstract] [Full Text] [PDF]