Journal article
Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia
Journal of lipid research, Vol.51(6), pp.1535-1545
06/2010
DOI: 10.1194/jlr.M002717
PMCID: PMC3035517
PMID: 20026666
Abstract
We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. LPL activity and mass in pre- and postheparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [
35
S]Methionine incorporation studies on adipose tissue showed that newly synthesized LPL was normal in size and normally glycosylated. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids being derived from de novo lipogenesis, rather than from the plasma lipoproteins. Given the delayed release of LPL into the plasma after heparin, we suspected that the chylomicronemia might be caused by mutations in
GPIHBP1
. Indeed, all three affected siblings were compound heterozygotes for missense mutations involving highly conserved cysteines in the Ly6 domain of GPIHBP1 (C65S and C68G). The mutant GPIHBP1 proteins reached the surface of transfected Chinese hamster ovary cells but were defective in their ability to bind LPL (as judged by both cell-based and cell-free LPL binding assays). Thus, the conserved cysteines in the Ly6 domain are crucial for GPIHBP1 function.
Details
- Title: Subtitle
- Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia
- Creators
- Gunilla Olivecrona - Department of Medical Biosciences/Physiological ChemistryEwa Ehrenborg - Department of Medicine, Karolinska Institute, Stockholm, SwedenHenrik Semb - Department of Medical Biosciences/Physiological ChemistryElena Makoveichuk - Department of Medical Biosciences/Physiological ChemistryAnna Lindberg - Department of Medical Biosciences/Physiological ChemistryMichael R Hayden - Departments of Medical Genetics and Medicine, University of British Columbia, Vancouver, CanadaPeter Gin - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CABrandon S. J Davies - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CAMichael M Weinstein - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CALoren G Fong - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CAAnne P Beigneux - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CAStephen G Young - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CAThomas Olivecrona - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CAOlle Hernell - Department of Clinical Sciences/Pediatrics, Umeå University, Umeå, Sweden
- Resource Type
- Journal article
- Publication Details
- Journal of lipid research, Vol.51(6), pp.1535-1545
- DOI
- 10.1194/jlr.M002717
- PMID
- 20026666
- PMCID
- PMC3035517
- NLM abbreviation
- J Lipid Res
- ISSN
- 0022-2275
- eISSN
- 1539-7262
- Publisher
- The American Society for Biochemistry and Molecular Biology
- Language
- English
- Date published
- 06/2010
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
- Record Identifier
- 9984024514102771
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