Dataset Information

Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.

ABSTRACT: In mice lacking glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), the LPL secreted by adipocytes and myocytes remains bound to heparan sulfate proteoglycans (HSPGs) on all cells within tissues. That observation raises a perplexing issue: Why isn't the freshly secreted LPL in wild-type mice captured by the same HSPGs, thereby preventing LPL from reaching GPIHBP1 on capillaries? We hypothesized that LPL-HSPG interactions are transient, allowing the LPL to detach and move to GPIHBP1 on capillaries. Indeed, we found that LPL detaches from HSPGs on cultured cells and moves to: 1) soluble GPIHBP1 in the cell culture medium; 2) GPIHBP1-coated agarose beads; and 3) nearby GPIHBP1-expressing cells. Movement of HSPG-bound LPL to GPIHBP1 did not occur when GPIHBP1 contained a Ly6 domain missense mutation (W109S), but was almost normal when GPIHBP1's acidic domain was mutated. To test the mobility of HSPG-bound LPL in vivo, we injected GPIHBP1-coated agarose beads into the brown adipose tissue of GPIHBP1-deficient mice. LPL moved quickly from HSPGs on adipocytes to GPIHBP1-coated beads, thereby depleting LPL stores on the surface of adipocytes. We conclude that HSPG-bound LPL in the interstitial spaces of tissues is mobile, allowing the LPL to move to GPIHBP1 on endothelial cells.

SUBMITTER: Allan CM

PROVIDER: S-EPMC5234724 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.

Allan Christopher M CM Larsson Mikael M Jung Rachel S RS Ploug Michael M Bensadoun André A Beigneux Anne P AP Fong Loren G LG Young Stephen G SG

Journal of lipid research 20161103 1

In mice lacking glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), the LPL secreted by adipocytes and myocytes remains bound to heparan sulfate proteoglycans (HSPGs) on all cells within tissues. That observation raises a perplexing issue: Why isn't the freshly secreted LPL in wild-type mice captured by the same HSPGs, thereby preventing LPL from reaching GPIHBP1 on capillaries? We hypothesized that LPL-HSPG interactions are transient, allowing the LPL to ...[more]

PMID: 27811232

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Dataset Information

Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.

Publications

Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.

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