The Acidic Domain of GPIHBP1 Is Important for the Binding of Lipoprotein Lipase and Chylomicrons

Peter Gin; Liya Yin; Brandon S. J Davies; Michael M Weinstein; Robert O Ryan; André Bensadoun; Loren G Fong; Stephen G Young; Anne P Beigneux

doi:10.1074/jbc.M802579200

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The Acidic Domain of GPIHBP1 Is Important for the Binding of Lipoprotein Lipase and Chylomicrons

Journal article

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The Acidic Domain of GPIHBP1 Is Important for the Binding of Lipoprotein Lipase and Chylomicrons

Peter Gin, Liya Yin, Brandon S. J Davies, Michael M Weinstein, Robert O Ryan, André Bensadoun, Loren G Fong, Stephen G Young and Anne P Beigneux

The Journal of biological chemistry, Vol.283(43), pp.29554-29562

10/24/2008

DOI: 10.1074/jbc.M802579200

PMCID: PMC2662032

PMID: 18713736

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Abstract

GPIHBP1, a glycosylphosphatidylinositol-anchored endothelial cell protein of the lymphocyte antigen 6 (Ly6) family, plays a key role in the lipolysis of triglyceride-rich lipoproteins ( e.g. chylomicrons). GPIHBP1 is expressed along the luminal surface of endothelial cells of heart, skeletal muscle, and adipose tissue, and GPIHBP1-expressing cells bind lipoprotein lipase (LPL) and chylomicrons avidly. GPIHBP1 contains an amino-terminal acidic domain (amino acids 24-48) that is enriched in aspartate and glutamate residues, and we previously speculated that this domain might be important in binding ligands. To explore the functional importance of the acidic domain, we tested the ability of polyaspartate or polyglutamate peptides to block the binding of ligands to pgsA-745 Chinese hamster ovary cells that overexpress GPIHBP1. Both polyaspartate and polyglutamate blocked LPL and chylomicron binding to GPIHBP1. Also, a rabbit antiserum against the acidic domain of GPIHBP1 blocked LPL and chylomicron binding to GPIHBP1-expressing cells. Replacing the acidic amino acids within GPIHBP1 residues 38-48 with alanine eliminated the ability of GPIHBP1 to bind LPL and chylomicrons. Finally, mutation of the positively charged heparin-binding domains within LPL and apolipoprotein AV abolished the ability of these proteins to bind to GPIHBP1. These studies indicate that the acidic domain of GPIHBP1 is important and that electrostatic interactions play a key role in ligand binding.

Lipids and Lipoproteins

Metabolism, Regulation, and Signaling

Details

Title: Subtitle: The Acidic Domain of GPIHBP1 Is Important for the Binding of Lipoprotein Lipase and Chylomicrons
Creators: Peter Gin - Departments of
Liya Yin - University of California, Los Angeles
Brandon S. J Davies - Departments of
Michael M Weinstein - Departments of
Robert O Ryan - Departments of
André Bensadoun - Departments of
Loren G Fong - Departments of
Stephen G Young - Departments of
Anne P Beigneux - Departments of
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.283(43), pp.29554-29562
DOI: 10.1074/jbc.M802579200
PMID: 18713736
PMCID: PMC2662032
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology
Language: English
Date published: 10/24/2008
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024566402771

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