Trial reportThe Journal of biological chemistry2014
Multimerization of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain.
Trial report in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.Journal of lipid research · 2025Article
- The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes.Journal of diabetes investigation · 2023Review
- Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A homozygous variant in theFrontiers in genetics · 2022Article
- The Importance of Lipoprotein Lipase Regulation in Atherosclerosis.Biomedicines · 2021Review
- The intrinsic instability of the hydrolase domain of lipoprotein lipase facilitates its inactivation by ANGPTL4-catalyzed unfolding.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity.Frontiers in cell and developmental biology · 2021Review
- Chylomicronemia from GPIHBP1 autoantibodies.Journal of lipid research · 2020Review
- Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- GPIHBP1 and Lipoprotein Lipase, Partners in Plasma Triglyceride Metabolism.Cell metabolism · 2019Review
- Evolution and Medical Significance of LU Domain-Containing Proteins.International journal of molecular sciences · 2019Review
- Did evolution create a flexible ligand-binding cavity in the urokinase receptor through deletion of a plesiotypic disulfide bond?The Journal of biological chemistry · 2019Article
- An upstream enhancer regulatesJournal of lipid research · 2019Article
- Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- An ELISA for quantifying GPIHBP1 autoantibodies and making a diagnosis of the GPIHBP1 autoantibody syndrome.Clinica chimica acta; international journal of clinical chemistry · 2018Article
- Emerging Roles of Vascular Endothelium in Metabolic Homeostasis.Circulation research · 2018Review
- Lipoprotein lipase reaches the capillary lumen in chickens despite an apparent absence of GPIHBP1.JCI insight · 2017Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.