GPIHBP1, an endothelial cell transporter for lipoprotein lipase

Journal of Lipid Research

Loren G. Fong¹  Brandon S.J. Davies²  Constance V. Voss³  André Bensadoun⁴  Michael M. Weinstein⁵  Peter Tontonoz⁵  Peter Gin⁵  Stephen G. Young⁵  Karen Reue⁶  Anne P. Beigneux⁶ 

[1] Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853;Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;To whom correspondence should be addressed.;Department of Pathology and Laboratory Medicine, Cornell University, Ithaca, NY 14853;Departments of Medicine, University of California, Los Angeles, CA 90095;Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;

关键词: chylomicrons;    endothelial cells;    lymphocyte antigen 6 proteins;    hypertriglyceridemia;    chylomicronemia;   

DOI  :  

来源: DOAJ

【 摘 要 】

Interest in lipolysis and the metabolism of triglyceride-rich lipoproteins was recently reignited by the discovery of severe hypertriglyceridemia (chylomicronemia) in glycosylphosphatidylinositol-anchored high density lipoprotein–binding protein 1 (GPIHBP1)-deficient mice. GPIHBP1 is expressed exclusively in capillary endothelial cells and binds lipoprotein lipase (LPL) avidly. These findings prompted speculation that GPIHBP1 serves as a binding site for LPL in the capillary lumen, creating “a platform for lipolysis.” More recent studies have identified a second and more intriguing role for GPIHBP1—picking up LPL in the subendothelial spaces and transporting it across endothelial cells to the capillary lumen. Here, we review the studies that revealed that GPIHBP1 is the LPL transporter and discuss which amino acid sequences are required for GPIHBP1–LPL interactions. We also discuss the human genetics of LPL transport, focusing on cases of chylomicronemia caused by GPIHBP1 mutations that abolish GPIHBP1’s ability to bind LPL, and LPL mutations that prevent LPL binding to GPIHBP1.

【 授权许可】

Unknown