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Molecular dissection of syndecan‐1 mediated triglyceride‐rich lipoprotein clearance
Author(s) -
Gonzales Jon C,
Foley Erin M,
Gordts Philip L,
Esko Jeffrey D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.792.2
Subject(s) - syndecan 1 , heparan sulfate , apolipoprotein b , apolipoprotein e , chemistry , biochemistry , mutant , receptor , lipoprotein , microbiology and biotechnology , biology , heparin , cell , medicine , cholesterol , gene , disease
Recently, genetic experiments in mice have confirmed that the heparan sulfate proteoglycan syndecan‐1 acts as a receptor for triglyceride‐rich lipoprotein (TRL) clearance in the liver. Binding depends on the heparan sulfate chains based on the accumulation of plasma TRLs in mice bearing mutations in heparan sulfate biosynthesis. To gain further insight into interaction of TRLs with syndecan‐1, we used an adenovirus reconstitution strategy. Reconstitution of mice lacking syndecan‐1 with virus containing wild‐type syndecan‐1 restored clearance in vivo, whereas viruses containing syndecan‐4 or mutant syndecan‐1 lacking the heparan sulfate chains did not. The intracellular C‐terminal domain also proved necessary for uptake. To identify the major apolipoprotein on the surface of TRLs that mediates binding to the heparan sulfate chains, we measured binding of TRLs isolated from mice lacking the major apolipoproteins, ApoB100, ApoB48, or ApoE. Particles derived from ApoE−/− mice did not bind, whereas no significant difference was noted in binding of ApoB100‐ and ApoB48‐ deficient TRLs compared to TRLs from wild‐type mice. These studies demonstrate that apoE is the dominant ligand for binding of TRLs to the heparan sulfate chains of syndecan‐1 and explains why dual deficiency of syndecan‐1 and LDL receptor results in a synergistic accumulation of plasma triglycerides.