Role of RAP in the biogenesis of lipoprotein receptors

The LDL receptor gene family is composed of several endocytic receptors that share structural homology and function in cellular uptake of various ligands including lipoprotein particles. The complex structure of these lipoprotein receptors is highlighted by the presence of clusters of cysteine-rich ligand-binding repeats. An important feature that is shared by all these receptors is the inhibition of ligand interaction by a 39-kDa receptor-associated protein (RAP). Recent studies have shown that under physiological conditions RAP serves as a molecular chaperone to assist the folding of lipoprotein receptors and their safe passage through the secretory pathway. Several non-exclusive models have been proposed regarding the molecular mechanisms of RAP function as an antagonist for ligand interaction with the receptors and as a molecular chaperone within the early secretory pathway. Elucidation of these mechanisms may provide insights into how biogenesis of lipoprotein receptors can be regulated via the expression of RAP under physiological and pathological conditions.