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https://hdl.handle.net/2440/34044
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Type: | Journal article |
Title: | Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation |
Author: | Russell, D. Doyle, K. Ochsner, S. Sandy, J. Richards, J. |
Citation: | Journal of Biological Chemistry, 2003; 278(43):42330-42339 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2003 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Darryl L. Russell, Kari M. H. Doyle, Scott A. Ochsner, John D. Sandy, and JoAnne S. Richards |
Abstract: | ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs-1) is a member of the ADAMTS family of metalloproteases which, together with ADAMTS-4 and ADAMTS-5, has been shown to degrade members of the lectican family of proteoglycans. ADAMTS-1 mRNA is induced in granulosa cells of periovulatory follicles by the luteinizing hormone surge through a progesterone receptor-dependent mechanism. Female progesterone receptor knockout (PRKO) mice are infertile primarily due to ovulatory failure and lack the normal periovulatory induction of ADAMTS-1 mRNA. We therefore investigated the protein localization and function of ADAMTS-1 in ovulating ovaries. Antibodies against two specific peptide regions, the pro-domain and the metalloprotease domain of ADAMTS-1, were generated. Pro-ADAMTS-1 of 110 kDa was identified in mural granulosa cells and appears localized to cytoplasmic secretory vesicles. The mature (85-kDa pro-domain truncated) form accumulated in the extracellular matrix of the cumulus oocyte complex (COC) during the process of matrix expansion. Each form of ADAMTS-1 protein increased >10-fold after the ovulatory luteinizing hormone surge in wild-type but not PRKO mice. Versican is also localized selectively to the ovulating COC matrix and was found to be cleaved yielding a 70-kDa N-terminal fragment immunopositive for the neoepitope DPEAAE generated by ADAMTS-1 and ADAMTS-4 protease activity. This extracellular processing of versican was reduced in ADAMTS-1-deficient PRKO mouse ovaries. These observations suggest that one function of ADAMTS-1 in ovulation is to cleave versican in the expanded COC matrix and that the anovulatory phenotype of PRKO mice is at least partially due to loss of this function. |
Keywords: | Granulosa Cells Oocytes Extracellular Matrix Animals Mice, Inbred C57BL Mice, Knockout Mice Enzyme Precursors Peptide Hydrolases Metalloendopeptidases Isoenzymes Disintegrins Lectins, C-Type Receptors, Progesterone Antibodies, Monoclonal Immunohistochemistry Tissue Distribution Ovulation Female ADAM Proteins Versicans Chondroitin Sulfate Proteoglycans ADAMTS1 Protein |
Description: | Copyright © 2003 by the American Society for Biochemistry and Molecular Biology. |
DOI: | 10.1074/jbc.M300519200 |
Published version: | http://www.jbc.org/cgi/content/abstract/278/43/42330 |
Appears in Collections: | Aurora harvest 6 Obstetrics and Gynaecology publications |
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