Molecular cloning of a lipolysis-stimulated remnant receptor expressed in the liver

The lipolysis-stimulated receptor (LSR) is a lipoprotein receptor primarily expressed in the liver and activated by free fatty acids. Antibodies inhib iting LSR functions showed that the receptor is a heterotrimer or tetramer consisting of 68-kDa (alpha) and 56-kDa (beta) sub units associated through disulfide bridges. Screening of expression libraries with these antibodies led to identification of mRNAs derived by alternate splicing from a single gene and coding for proteins with molecular masses matching that of LSR al pha and beta, Antibodies directed against a synthetic peptide of LSR alpha and beta putative ligand binding domains inhibited LSR activity. Western bl otting identified two liver proteins with the same apparent molecular mass as that of LSR alpha and beta. Transient transfections of LSR alpha alone i n Chinese hamster ovary cells increased oleate-induced binding and uptake o f lipoproteins, while cotransfection of both LSR alpha and beta increased o leate-induced proteolytic degradation of the particles. The ligand specific ity of LSR expressed in cotransfected Chinese hamster ovary cells closely m atched that previously described using fibroblasts from subjects lacking th e low density lipoprotein receptor. LSR affinity is highest for the triglyc eride-rich lipoproteins, chylomicrons, and very low density lipoprotein. We speculate that LSR is a rate-limiting step for the clearance of dietary tr iglycerides and plays a role in determining their partitioning between the liver and peripheral tissues.