The mutant Asn291 → Ser human lipoprotein lipase is associated with reduced catalytic activity and does not influence binding to heparin

FEBS Letters

Buscà, Roser²  Vilella, Elisabeth³  Deeb, Samir S⁴  Peinado, Julia¹  Auwerx, Johan⁵  Reina, Manuel²  Vilaró, Senén² 

[1] Biochemistry and Molecular Biology Department, University of Barcelona, Diagonal 645, 08028 Barcelona, Spain;Department of Cell Biology, University of Barcelona, Diagonal 645, 08028 Barcelona, Spain;Biomedical Research Center, Hosp. St. Joan, St. Joan St. sln, 43201 Reus, Tarragona, Spain;Departments of Genetics and Medicine, University of Washington, Seattle, WA 98195, USA;Laboratoire de Biologie des Régulations chez les Eucaryotes, Dept. d'Athérosclerose, Institut Pasteur, Rue Calmette, 59019 Lille, Spain

关键词: Hypertriglyceridemia;    Lipoprotein lipase;    Mutation;    LPL;    lipoprotein lipase;    hLPL;    human lipoprotein lipase;    ER;    rough endoplasmic reticulum;   

DOI  :  10.1016/0014-5793(95)00582-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lipoprotein lipase (LPL) plays a central role in triglyceride metabolism, regulating the catabolism of triglyceride-rich lipoprotein particles. LPL performs its hydrolytic action attached to heparan sulfate proteoglycans at the luminal surface of capillary endothelial cells. We have assessed the effect of the Asn²⁹¹ → Ser (N291S) substitution found in LPL gene from a human hyperlipemic patient. Our results showed that both the wild-type (WT) and N291S hLPL expressed in COS1 cells were secreted to the extracellular medium, and presented similar intracellular distibution patterns. Furthermore, heparin-Sepharose affinity chromatography assays revealed normal heparin affinity of the N291S hLPL. In addition, both the mutant and the WT protein bound to the surface of human fibroblasts and untransfected COS1 cells. Interestingly, disminished LPL specific activity was observed in the extracellular medium from mutant expressing cells. Therefore the lack of normal LPL activity in patients harbouring such a mutation could be the cause of their hyperlipemic disorder.

【 授权许可】

Unknown