TY - JOUR
T1 - Mobility of “HSPG-bound” LPL explains how LPL is able to reach GPIHBP1 on capillaries
AU - Allan, Christopher M
AU - Larsson, Mikael
AU - Jung, Rachel S
AU - Ploug, Michael
AU - Bensadoun, André
AU - Beigneux, Anne P
AU - Fong, Loren G
AU - Young, Stephen G
N1 - Copyright © 2016, The American Society for Biochemistry and Molecular Biology.
PY - 2017/1
Y1 - 2017/1
N2 - In mice lacking glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPI- HBP1), 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.-Allan, C. M., M. Larsson, R. S. Jung, M. Ploug, A. Bensadoun, A. P. Beigneux, L. G. Fong, and S. G. Young. Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.
AB - In mice lacking glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPI- HBP1), 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.-Allan, C. M., M. Larsson, R. S. Jung, M. Ploug, A. Bensadoun, A. P. Beigneux, L. G. Fong, and S. G. Young. Mobility of "HSPG-bound" LPL explains how LPL is able to reach GPIHBP1 on capillaries.
U2 - 10.1194/jlr.m072520
DO - 10.1194/jlr.m072520
M3 - Journal article
C2 - 27811232
SN - 0022-2275
VL - 58
SP - 216
EP - 225
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 1
ER -