ABSTRACT

-Macroglobulin (M), a major plasma component in all vertebrates, is proposed to function as a broad spectrum protease inhibitor. The M-proteinase complex (activated M; M) is removed rapidly by receptor-mediated endocytosis in the liver. Here we demonstrate by Western blotting that M is also present in the yolk of chicken oocytes. Plasma levels of M are increased by estrogen, and yolk M is partially proteolyzed, consistent with the action of cathepsin D on endocytosed M. Two known estrogen-induced ligands of the oocyte-specific 95-kDa very low density lipoprotein/vitellogenin receptor (OVR) are also fragmented by yolk cathepsin D (Retzek, H., Steyrer, E., Sanders, E. J., Nimpf, J., and Schneider, W. J.(1992) DNA Cell Biol. 11, 661-672). Since these findings suggested a common uptake mechanism for lipoproteins and M by oocytes, we investigated whether OVR, a member of the low density lipoprotein receptor family, functions in the metabolism of M. Ligand blotting of oocyte membrane extracts with chicken M revealed that it binds to OVR. Surprisingly, the oocyte receptor also recognizes native M, in sharp contrast to the hepatic receptor, which only binds M. Receptor interaction of both forms requires Ca; however, competition experiments suggest that M and M interact with slightly different, or overlapping, sites on the receptor. Colocalization of M and OVR in coated vesicles isolated from growing oocytes, and internalization and degradation of methylamine-activated M by COS-7 cells transfected with OVR, strongly suggest that M is transported into growing oocytes via OVR. We propose that this multifunctional receptor mediates pathways at the metabolic crossroads of lipoproteins and protease inhibitor complexes.

FOOTNOTES

*

These studies were supported in part by Grants P-9040-MOB and P-9508-MOB from the Austrian Science Foundation (FWF) (to W. J. S. and J. N.) and by Grant EECBMH1-CT93-1088 from the European Community (to W. J. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

Supported by the Danish Science Research Council.

¶

Supported by a Lise Meitner postdoctoral fellowship from the Austrian Science Foundation (FWF).

**

To whom correspondence should be addressed: Dept. of Molecular Genetics, University and Biocenter Vienna, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria. Tel.: 43-1-79515-2111; Fax: 43-1-79515-2900

()

The abbreviations used are: (V)LDL, (very) low density lipoprotein; VTG, vitellogenin; OVR, oocyte very low density lipoprotein/vitellogenin receptor; apo, apolipoprotein; M, -macroglobulin; MR, M receptor; M*, protease-activated M; MMA, methylamine-treated M; LRP, LDL receptor-related protein; PEG, polyethylene glycol; PAGE, polyacrylamide gel electrophoresis; MES, 4-morpholineethanesulfonic acid.

()

H. Bujo, personal communication.

ACKNOWLEDGEMENTS

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Hummel, S. Christian, A. Osanger, H. Heid, J. Nimpf, and W. J. Schneider Identification of a Novel Chondroitin-sulfated Collagen in the Membrane Separating Theca and Granulosa Cells in Chicken Ovarian Follicles: THE GRANULOSA-THECA CELL INTERFACE IS NOT A BONA FIDE BASEMENT MEMBRANE J. Biol. Chem., March 16, 2007; 282(11): 8011 - 8018. [Abstract] [Full Text] [PDF]

				C. Britton and L. Murray Cathepsin L protease (CPL-1) is essential for yolk processing during embryogenesis in Caenorhabditis elegans J. Cell Sci., October 1, 2004; 117(21): 5133 - 5143. [Abstract] [Full Text] [PDF]

				N. Hiramatsu, R. W. Chapman, J. K. Lindzey, M. R. Haynes, and C. V. Sullivan Molecular Characterization and Expression of Vitellogenin Receptor from White Perch (Morone americana) Biol Reprod, June 1, 2004; 70(6): 1720 - 1730. [Abstract] [Full Text] [PDF]

				Y. Zhou, J. Zhang, and M. L. King Xenopus Autosomal Recessive Hypercholesterolemia Protein Couples Lipoprotein Receptors with the AP-2 Complex in Oocytes and Embryos and Is Required for Vitellogenesis J. Biol. Chem., November 7, 2003; 278(45): 44584 - 44592. [Abstract] [Full Text] [PDF]

				S.-J. Seo, H.-M. Cheon, J. Sun, T. W. Sappington, and A. S. Raikhel Tissue- and Stage-specific Expression of Two Lipophorin Receptor Variants with Seven and Eight Ligand-binding Repeats in the Adult Mosquito J. Biol. Chem., October 24, 2003; 278(43): 41954 - 41962. [Abstract] [Full Text] [PDF]

				M. G. Mahon, K. A. Lindstedt, M. Hermann, J. Nimpf, and W. J. Schneider Multiple Involvement of Clusterin in Chicken Ovarian Follicle Development. BINDING TO TWO OOCYTE-SPECIFIC MEMBERS OF THE LOW DENSITY LIPOPROTEIN RECEPTOR GENE FAMILY J. Biol. Chem., February 12, 1999; 274(7): 4036 - 4044. [Abstract] [Full Text] [PDF]

				W. Stockinger, E. Hengstschlager-Ottnad, S. Novak, A. Matus, M. Huttinger, J. Bauer, H. Lassmann, W. J. Schneider, and J. Nimpf The Low Density Lipoprotein Receptor Gene Family. DIFFERENTIAL EXPRESSION OF TWO alpha 2-MACROGLOBULIN RECEPTORS IN THE BRAIN J. Biol. Chem., November 27, 1998; 273(48): 32213 - 32221. [Abstract] [Full Text] [PDF]

				J. Magrané, M. Reina, R. Pagan, A. Luna, R. P. Casaroli-Marano, B. Angelin, M. Gåfvels, and S. Vilaró Bovine aortic endothelial cells express a variant of the very low density lipoprotein receptor that lacks the O-linked sugar domain J. Lipid Res., November 1, 1998; 39(11): 2172 - 2181. [Abstract] [Full Text]

				M. Hermann, K. A. Lindstedt, R. Foisner, S. Mörwald, M. G. Mahon, R. Wandl, W. J. Schneider, and J. Nimpf Apolipoprotein A-I production by chicken granulosa cells FASEB J, July 1, 1998; 12(10): 897 - 903. [Abstract] [Full Text]

				S. Morwald, H. Yamazaki, H. Bujo, J. Kusunoki, T. Kanaki, K. Seimiya, N. Morisaki, J. Nimpf, W. J. Schneider, and Y. Saito A Novel Mosaic Protein Containing LDL Receptor Elements Is Highly Conserved in Humans and Chickens Arterioscler. Thromb. Vasc. Biol., May 1, 1997; 17(5): 996 - 1002. [Abstract] [Full Text]

				H. Bujo, M. Hermann, K. A. Lindstedt, J. Nimpf, and W. J. Schneider Low Density Lipoprotein Receptor Gene Family Members Mediate Yolk Deposition J. Nutr., May 1, 1997; 127 (5): 801S - 801S. [Abstract] [Full Text] [PDF]

				T. Hiesberger, R. Hodits, R. Ullrich, M. Exner, D. Kerjaschki, W. J. Schneider, and J. Nimpf Receptor-associated Protein and Members of the Low Density Lipoprotein Receptor Family Share a Common Epitope. AN EXTENDED MODEL FOR THE DEVELOPMENT OF PASSIVE HEYMANN NEPHRITIS J. Biol. Chem., November 15, 1996; 271(46): 28792 - 28797. [Abstract] [Full Text] [PDF]

				H. Yamazaki, H. Bujo, J. Kusunoki, K. Seimiya, T. Kanaki, N. Morisaki, W. J. Schneider, and Y. Saito Elements of Neural Adhesion Molecules and a Yeast Vacuolar Protein Sorting Receptor Are Present in a Novel Mammalian Low Density Lipoprotein Receptor Family Member J. Biol. Chem., October 4, 1996; 271(40): 24761 - 24768. [Abstract] [Full Text] [PDF]

				S. Novak, T. Hiesberger, W. J. Schneider, and J. Nimpf A New Low Density Lipoprotein Receptor Homologue with 8 Ligand Binding Repeats in Brain of Chicken and Mouse J. Biol. Chem., May 17, 1996; 271(20): 11732 - 11736. [Abstract] [Full Text] [PDF]

				K. M. Argraves, F. D. Battey, C. D. MacCalman, K. R. McCrae, M. Gåfvels, K. F. Kozarsky, D. A. Chappell, J. F. Strauss , III, and D. K. Strickland The Very Low Density Lipoprotein Receptor Mediates the Cellular Catabolism of Lipoprotein Lipase and Urokinase-Plasminogen Activator Inhibitor Type I Complexes J. Biol. Chem., November 3, 1995; 270(44): 26550 - 26557. [Abstract] [Full Text] [PDF]

				R. A. Hodits, J. Nimpf, D. M. Pfistermueller, T. Hiesberger, W. J. Schneider, T. J. Vaughan, K. S. Johnson, M. Haumer, E. Kuechler, G. Winter, et al. An Antibody Fragment from a Phage Display Library Competes for Ligand Binding to the Low Density Lipoprotein Receptor Family and Inhibits Rhinovirus Infection J. Biol. Chem., October 13, 1995; 270(41): 24078 - 24085. [Abstract] [Full Text] [PDF]

				H. Bujo, K. A. Lindstedt, M. Hermann, L. M. Dalmau, J. Nimpf, and W. J. Schneider Chicken Oocytes and Somatic Cells Express Different Splice Variants of a Multifunctional Receptor J. Biol. Chem., October 6, 1995; 270(40): 23546 - 23551. [Abstract] [Full Text] [PDF]

				T. Hiesberger, M. Hermann, L. Jacobsen, S. Novak, R. A. Hodits, H. Bujo, M. Meilinger, M. Httinger, W. J. Schneider, and J. Nimpf The Chicken Oocyte Receptor for Yolk Precursors as a Model for Studying the Action of Receptor-associated Protein and Lactoferrin J. Biol. Chem., August 4, 1995; 270(31): 18219 - 18226. [Abstract] [Full Text] [PDF]

				M. Hermann, M. G. Mahon, K. A. Lindstedt, J. Nimpf, and W. J. Schneider Lipoprotein Receptors in Extraembryonic Tissues of the Chicken J. Biol. Chem., May 26, 2000; 275(22): 16837 - 16844. [Abstract] [Full Text] [PDF]

				C. Brandes, L. Kahr, W. Stockinger, T. Hiesberger, W. J. Schneider, and J. Nimpf Alternative Splicing in the Ligand Binding Domain of Mouse ApoE Receptor-2 Produces Receptor Variants Binding Reelin but Not alpha 2-Macroglobulin J. Biol. Chem., June 15, 2001; 276(25): 22160 - 22169. [Abstract] [Full Text] [PDF]