GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding.

ABSTRACT:

Rationale

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia.

Objective

We sought to understand mechanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia.

Methods and results

We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and Drosophila S2 cells. In each expression system, mutation of cysteines in GPIHBP1's Ly6 domain (including mutants identified in patients with chylomicronemia) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization/multimerization was not

SUBMITTER: Beigneux AP 

PROVIDER: S-EPMC4329087 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature