Common sequence variants of lipoprotein lipase: Standardized studies of in vitro expression and catalytic function

Hanfang Zhang, Howard Henderson, S. Eric Gagne, Susanne M. Clee, Li Miao, Guoqing Liu, Michael R. Hayden

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

We have assessed the functional activity of three common sequence variants of human lipoprotein lipase (LPL). Two of these, Asn291Ser and Asp9Asn arise from missense mutations while the third, Ser447Ter; derives from a nonsense mutation, truncating LPL by two residues. As previous in vitro studies have produced conflicting results, we have re-analyzed the catalytic function of these variants using the COS cell transfection system, under optimized and standardized experimental protocols. We found the Asn291Ser variant to manifest with a decrease in catalytic activity (57% of normal) due to a reduction in secretion and stability of the active homodimeric form. The Asp9Asn variant also showed a significant decrease in catalytic activity (85% of normal), but this was found to be due to a decreased rate of secretion only, as the homodimeric form was stable. The findings for these mutants contrasted with those of the Ser447Ter truncation variant which proved to be catalytically normal; this variant also manifested normal homodimer stability. The truncated variant did however, present with a higher total secreted mass level (131%) than control LPL. This was most likely due to enhanced secretion of the monomeric form. None of these mutations exhibited defects in binding affinity to cell surface proteoglycans. Each of these variants deviated significantly from normal as regards to their secreted activity or mass levels in the COS cell transfection system.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalBiochimica et Biophysica Acta - Lipids and Lipid Metabolism
Volume1302
Issue number2
DOIs
StatePublished - Jul 26 1996

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Lipoprotein Lipase
COS Cells
Transfection
Catalyst activity
Nonsense Codon
Missense Mutation
Proteoglycans
Defects
Mutation
In Vitro Techniques
human LPL protein

Keywords

  • Gene variant
  • Hyperlipidemia
  • Lipoprotein lipase
  • Transfection

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

Cite this

Common sequence variants of lipoprotein lipase : Standardized studies of in vitro expression and catalytic function. / Zhang, Hanfang; Henderson, Howard; Gagne, S. Eric; Clee, Susanne M.; Miao, Li; Liu, Guoqing; Hayden, Michael R.

In: Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, Vol. 1302, No. 2, 26.07.1996, p. 159-166.

Research output: Contribution to journalArticle

Zhang, Hanfang ; Henderson, Howard ; Gagne, S. Eric ; Clee, Susanne M. ; Miao, Li ; Liu, Guoqing ; Hayden, Michael R. / Common sequence variants of lipoprotein lipase : Standardized studies of in vitro expression and catalytic function. In: Biochimica et Biophysica Acta - Lipids and Lipid Metabolism. 1996 ; Vol. 1302, No. 2. pp. 159-166.
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