In addition to its ability to remove cholesterol from cells, HDL also delivers cholesterol to cells through a poorly defined process in which cholesteryl esters are selectively transferred from HDL particles into the cell without the uptake and degradation of the lipoprotein particle. The HDLcholesteryl ester selective uptake pathway is known to occur in human, rabbit, and rodent hepatocytes where it may contribute to the clearance of plasma cholesteryl ester. The selective uptake pathway has been studied most extensively in steroidogenic cells of rodents in which it accounts for 90% or more of the cholesterol destined for steroid production or cholesteryl ester accumulation. In this study we have used apo A-I-, apo A-II-, and apo E-deficient mice created by gene targeting in embryonic stem cells to test the importance of the three major HDL proteins in determining cholesteryl ester accumulation in steroidogenic cells of the adrenal gland, ovary, and testis. apo E and apo A-II deficiencies were found to have only modest effects on cholesteryl ester accumulation. In contrast, apo A-I deficiency caused an almost complete failure to accumulate cholesteryl ester in steroidogenic cells. These results suggest that apo A-I is essential for the selective uptake of HDL-cholesteryl esters. The lack of apo A-I has a major impact on adrenal gland physiology causing diminished basal corticosteroid production, a blunted steroidogenic response to stress, and increased expression of compensatory pathways to provide cholesterol substrate for steroid production. ( J. Clin. Invest. 1996. 97: 2660-2671.) Key words: high density lipoprotein • selective uptake • corticosteroids • apolipoprotein-deficient mice
Fertilization depends on cell surface recognition proteins that interact and thereby mediate binding and subsequent fusion of the sperm and egg. Overlapping complementary DNA's encoding the egg plasma membrane receptor for sperm from the sea urchin Strongylocentrotus purpuratus were cloned and sequenced. Analysis of the deduced primary structure suggests that the receptor is a transmembrane protein with a short cytoplasmic domain. This domain showed no sequence similarity to known protein sequences. In contrast, the extracellular, sperm binding domain of the receptor did show sequence similarity to the heat shock protein 70 (hsp70) family of proteins. Recombinant protein representing this portion of the receptor bound to the sperm protein, binding, and also inhibited fertilization in a species-specific manner; beads coated with the protein became specifically bound to acrosome-reacted sperm. These data provide a basis for detailed investigations of molecular interactions that occur in gamete recognition and egg activation.
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