THE SOMATIC CELL-SPECIFIC LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN OF THE CHICKEN - CLOSE KINSHIP TO MAMMALIAN LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE FAMILY MEMBERS

Recently, the family of mammalian genes homologous to that for the low density lipoprotein (LDL) receptor has grown. One of the new family m embers, termed LDL receptor-related protein/alpha2-macroglobulin recep tor (LRP/alpha2MR), is one of the largest cell surface proteins charac terized to date. Its functions have been hypothesized to include the p lasma clearance of chylomicron remnants and activated alpha2-macroglob ulin, as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Here we describe the mole cular characterization of an LRP/alpha2MR expressed in chickens, which do not metabolize chylomicron remnants. This chicken protein is expre ssed in somatic tissues and is different from a second LRP/alpha2MR ex clusively expressed in growing ovarian follicles. The sequence of the somatic cell-specific chicken LRP/alpha2MR, deduced from cloned full-l ength cDNA, shows 83% overall identity with human LRP/alpha2MR. Import ant characteristic features of the modular protein are completely cons erved; in particular, all cysteine residues align perfectly. The avian LRP/alpha2MR is post-translationally cleaved in the same fashion as i ts human counterpart, and the resulting 515-kDa extracellular subunit binds Ca2+, alpha2-macroglobulin, and vitellogenin. The results indica te that avian LRP/alpha2MR genes have emerged from an ancestor designe d to ensure a pivotal event in the reproduction of oviparous species, i.e. vitellogenesis, and that mammalian LRP/alpha2MRs have acquired fe atures required for functioning in plasma clearance of certain non-yol k proteins.