期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：21
页码：11830-11835
DOI：10.1073/pnas.96.21.11830
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：CD9 is a tetraspan protein that associates with several {beta}1 integrins, including 6{beta}1. Because 6{beta}1 is present on murine eggs and interacts with the sperm-surface glycoprotein ADAM 2 (fertilin {beta}), we first asked whether CD9 is present on murine eggs and whether it functions in sperm-egg binding and fusion. CD9 is present on the plasma membrane of oocytes in the ovary as well as on eggs isolated from the oviduct. The anti-CD9 mAb, JF9, potently inhibits sperm-egg binding and fusion in vitro in a dose-dependent manner. JF9 also disrupts binding of fluorescent beads coated with native fertilin or a recombinant fertilin {beta} disintegrin domain. (Both ligands bind to the egg via 6{beta}1.) Immunohistochemistry showed that CD9 is undetectable in the uterine epithelium, appears basolaterally and as prominent apical patches on the epithelium in the region between the uterus and the oviduct, and then persists apically in the oviduct. The integrin 6A subunit is found in similar apical patches in the region between the uterus and oviduct, but is confined to the basal aspect of the epithelium in the uterus and oviduct. Hence, 6A and CD9 both are expressed on the apical epithelial surface at the uterine-oviduct junction. These findings correlate with the observation that fertilin {beta} "knockout" sperm traverse the uterus but do not progress into the oviduct, contributing to the infertility of fertilin {beta}-/- male mice. Our results suggest that high-avidity binding between fertilin {beta} (ADAM 2) and 6{beta}1 requires cooperation between 6{beta}1 and CD9. Such cooperation may assist sperm passage into the oviduct as well as sperm-egg interactions.
