Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia

Hayden, Michael R (author)

Gin, Peter (author)

Davies, Brandon S J (author)

Weinstein, Michael M (author)

Fong, Loren G (author)

Beigneux, Anne P (author)

Young, Stephen G (author)

(creator_code:org_t)

New York : Rockefeller U.P. 2010
2010
English.
In: Journal of Lipid Research. - New York : Rockefeller U.P.. - 0022-2275 .- 1539-7262. ; 51:6, s. 1535-1545

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. Lipoprotein lipase (LPL) activity and mass in pre- and post-heparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [35S]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 CHO 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.

By the author/editor: Olivecrona, Guni ...; Ehrenborg, Ewa; Semb, Henrik; Makoveichuk, Ele ...; Lindberg, Anna; Hayden, Michael ...; show more...; Gin, Peter; Davies, Brandon ...; Weinstein, Micha ...; Fong, Loren G; Beigneux, Anne P; Young, Stephen G; Olivecrona, Thom ...; Hernell, Olle; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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