Cubbing in proapolipoprotein maturation.

Journal of Lipid Research Volume 52, 2011 1861 Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc. In this issue of the Journal of Lipid Research , Francone and colleagues ( 1 ) have described an interesting HDL phenotype in a mouse defi cient in procollagen proteinase enhancer 2 (PCPE2). Present in the plasma of the mice are pre HDL containing as its major, if not only, apolipoprotein pro-apoA-I, accompanied by the accumulation of an enlarged HDL also containing predominantly pro-apoA-I. This highlights a potentially new actor in the regulation of HDL homeostasis. Recent genetic association studies have suggested that PCPE2 variation may be weakly associated with HDL levels. The phenotype described in the Francone paper, while of great interest, is not readily understandable in all of its details. In addition, this study raises some fascinating evolutionary and physiological questions: a ) How and where is the apoA-I proprotein converted to the mature protein? What is the biochemical mechanism for this conversion? b ) What is the functional role of the secretion of apoA-I as a proprotein? c ) Does the proprotein differ from the mature protein in its function and regulation of cholesterol homeostasis? d ) What is the mechanism for the accumulation of an enlarged HDL containing pro-apoA-I? How does this HDL compare in function to HDL in which mature apoA-I is the predominant apoprotein?