THE CHICKEN OOCYTE RECEPTOR FOR LIPOPROTEIN DEPOSITION RECOGNIZES ALPHA(2)-MACROGLOBULIN

alpha(2)-Macroglobulin (alpha(2)M), a major plasma component in all ve rtebrates, is proposed to function as a broad spectrum protease inhibi tor. The alpha(2)M-proteinase complex (activated alpha(2)M; alpha(2)M ) is removed rapidly by receptor-mediated endocytosis in the liver. He re we demonstrate by Western blotting that alpha(2)M is also present i n the yolk of chicken oocytes. Plasma levels of alpha(2)M are increase d by estrogen, and yolk alpha(2)M is partially proteolyzed, consistent with the action of cathepsin D on endocytosed alpha(2)M. Two known es trogen-induced ligands of the oocyte-specific 95-kDa very low density lipoprotein/vitellogenin receptor (OVR) are also fragmented by yolk ca thepsin D (Retzek, H., Steyrer, E., Sanders, E. J., Nimpf, J., and Sch neider, W. J. (1992) DNA Cell Biol. 11, 661-672). Since these findings suggested a common uptake mechanism for lipoproteins and alpha(2)M by oocytes, we investigated whether OVR, a member of the low density lip oprotein receptor family, functions in the metabolism of alpha(2)M. Li gand blotting of oocyte membrane extracts with chicken alpha(2)M reve aled that it binds to OVR. Surprisingly, the oocyte receptor also reco gnizes native alpha(2)M, in sharp contrast to the hepatic receptor, wh ich only binds alpha(2)M. Receptor interaction of both forms requires Ca2+; however, competition experiments suggest that alpha(2)M and alp ha(2)M interact with slightly different, or overlapping, sites on the receptor. Colocalization of alpha(2)M and OVR in coated vesicles isol ated from growing oocytes, and internalization and degradation of meth ylamine-activated alpha(2)M by COS 7 cells transfected with OVR, stron gly suggest that alpha(2)M is transported into growing oocytes via OVR . We propose that this multifunctional receptor mediates pathways at t he metabolic crossroads of lipoproteins and protease inhibitor complex es.