GPIHBP1 Is Responsible for the Entry of Lipoprotein Lipase into Capillaries

被引:305
作者
Davies, Brandon S. J. [1 ]
Beigneux, Anne P. [1 ]
Barnes, Richard H., II [1 ]
Tu, Yiping [1 ]
Gin, Peter [1 ]
Weinstein, Michael M. [2 ]
Nobumori, Chika [1 ]
Nyren, Rakel [3 ]
Goldberg, Ira [4 ]
Olivecrona, Gunilla [3 ]
Bensadoun, Andre [5 ]
Young, Stephen G. [1 ,2 ]
Fong, Loren G. [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[3] Umea Univ, Dept Med Biosci Physiol Chem, S-90187 Umea, Sweden
[4] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[5] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
基金
美国国家卫生研究院;
关键词
GPI-ANCHORED PROTEINS; ADIPOSE-TISSUE; CELL-SURFACE; RECEPTOR; BINDING; CHYLOMICRONEMIA; PLASMA; MICE; GENE;
D O I
10.1016/j.cmet.2010.04.016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.
引用
收藏
页码:42 / 52
页数:11
相关论文
共 26 条
  • [1] Plasmalemmal caveolae and GPI-anchored membrane proteins
    Anderson, Richard G. W.
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1993, 5 (04) : 647 - 652
  • [2] Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons
    Beigneux, Anne P.
    Davies, Brandon S. J.
    Gin, Peter
    Weinstein, Michael M.
    Farber, Emily
    Qiao, Xin
    Peale, Franklin
    Bunting, Stuart
    Walzem, Rosemary L.
    Wong, Jinny S.
    Blaner, William S.
    Ding, Zhi-Ming
    Melford, Kristan
    Wongsiriroj, Nuttaporn
    Shu, Xiao
    de Sauvage, Fred
    Ryan, Robert O.
    Fong, Loren G.
    Bensadoun, Andre
    Young, Stephen G.
    [J]. CELL METABOLISM, 2007, 5 (04) : 279 - 291
  • [3] Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase
    Beigneux, Anne P.
    Gin, Peter
    Davies, Brandon S. J.
    Weinstein, Michael M.
    Bensadoun, Andre
    Fong, Loren G.
    Young, Stephen G.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (44) : 30240 - 30247
  • [4] Chylomicronemia With a Mutant GPIHBP1 (Q115P) That Cannot Bind Lipoprotein Lipase
    Beigneux, Anne P.
    Franssen, Remco
    Bensadoun, Andre
    Gin, Peter
    Melford, Kristan
    Peter, Jorge
    Walzem, Rosemary L.
    Weinstein, Michael M.
    Davies, Brandon S. J.
    Kuivenhoven, Jan A.
    Kastelein, John J. P.
    Fong, Loren G.
    Dallinga-Thie, Geesje M.
    Young, Stephen G.
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (06) : 956 - U447
  • [5] SORTING OF GPI-ANCHORED PROTEINS TO GLYCOLIPID-ENRICHED MEMBRANE SUBDOMAINS DURING TRANSPORT TO THE APICAL CELL-SURFACE
    BROWN, DA
    ROSE, JK
    [J]. CELL, 1992, 68 (03) : 533 - 544
  • [6] Brunzell JD., 2001, METABOLIC MOL BASES, V8th, P2789
  • [7] EFFECT OF NUTRITIONAL-STATUS ON RAT ADIPOSE-TISSUE, MUSCLE AND POST-HEPARIN PLASMA CLEARING FACTOR LIPASE ACTIVITIES - THEIR RELATIONSHIP TO TRIGLYCERIDE FATTY-ACID UPTAKE BY FAT-CELLS AND TO PLASMA-INSULIN CONCENTRATIONS
    CRYER, A
    RILEY, SE
    WILLIAMS, ER
    ROBINSON, DS
    [J]. CLINICAL SCIENCE AND MOLECULAR MEDICINE, 1976, 50 (03): : 213 - 221
  • [8] The Expression of GHIBP1, an Endothelial Cell Binding Site for Lipoprotein Lipase and Chylomicrons, Is Induced by Peroxisome Proliferator-Activated Receptor-γ
    Davies, Brandon S. J.
    Waki, Hironori
    Beigneux, Anne P.
    Farber, Emily
    Weinstein, Michael M.
    Wilpitz, Damien C.
    Tai, Li-Jung
    Evans, Ronald M.
    Fong, Loren G.
    Tontonoz, Peter
    Young, Stephen G.
    [J]. MOLECULAR ENDOCRINOLOGY, 2008, 22 (11) : 2496 - 2504
  • [9] Chylomicronemia With Low Postheparin Lipoprotein Lipase Levels in the Setting of GPIHBP1 Defects
    Franssen, Remco
    Young, Stephen G.
    Peelman, Frank
    Hertecant, Jozef
    Sierts, Jeroen A.
    Schimmel, Alinda W. M.
    Bensadoun, Andre
    Kastelein, John J. P.
    Fong, Loren G.
    Dallinga-Thie, Geesje M.
    Beigneux, Anne P.
    [J]. CIRCULATION-CARDIOVASCULAR GENETICS, 2010, 3 (02) : 169 - 178
  • [10] NORMAL PLASMA-LIPOPROTEINS AND FERTILITY IN GENE-TARGETED MICE HOMOZYGOUS FOR A DISRUPTION IN THE GENE ENCODING VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR
    FRYKMAN, PK
    BROWN, MS
    YAMAMOTO, T
    GOLDSTEIN, JL
    HERZ, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) : 8453 - 8457