title: GPIHBP1, an endothelial cell transporter for lipoprotein lipase.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA 90095, USA. sgyoung@mednet.ucla.edu
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Brandon S J
authors.initials: BS
authors.lastname: Davies
authors.forename: Constance V
authors.initials: CV
authors.lastname: Voss
authors.forename: Peter
authors.initials: P
authors.lastname: Gin
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weinstein
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D018110:Receptors, Lipoprotein
chemical_list: D002352:Carrier Proteins; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase