Normal fertilization occurs with eggs lacking the integrin α6β1 and is CD9-dependent
Normal fertilization occurs with eggs lacking the integrin α6β1 and is CD9-dependent
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DOI：
10.1083/jcb.149.6.1289
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发表时间：
2000-06-12
影响因子：
7.8
通讯作者：
Myles, DG
中科院分区：
文献类型：
--
作者：
Miller, BJ;Georges-Labouesse, E;Myles, DG
先前基于抗α6整合素单抗(GoH3)抑制受精的结果表明，小鼠卵子上的α6β1整合素作为精子的受体发挥作用(Almeida，E.A.，A.P.Huovila，A.E.Sutherland)。L.E.斯蒂芬斯PG.题名/责任者：The First of China/J.1995年。牢房。81：1095-1103)。因为卵表面的Tetraspanin CD9是配子融合所必需的(Kaji，K.，S.Oda，T.Shikano，T.Ohnuki，Y.Uematsu)。作者：J.Sakagami，N.Tada，S.Miyazaki，A.2000年。纳特。吉内。24：279-282；勒瑙尔。作者：C.2000年。科学。287：319-321；Miyado，II.，G.Yamada，S.Yamada，H.Hasuwa，Y.Nakamura，F.Ryu II.铃木、K.小井、K.Inoue、A.Ogura、M.Okabe和E.Mekada。2000年。科学。287：321-324)和CD9被认为与整合素相关，最近的配子融合模型假设鸡蛋CD9在融合中与α6β1相关(Chen，M.S.，K.S.童，S.A.Coonrod，Y.Takahashi，D.Bigler，A.Chang，Y.1999年。程序娜塔莉。阿卡德。SCI。美国。96：11830-11835，Kaji，K.，S.Oda，T.Shikano，T.Ohnuki，Y.Uematsu，J.Sakagami，N.Tada，S.Miyazaki和A.Kudo。2000年。纳特。吉内。24：279-282；Le Naour，E，E.Rubinstein，C.Jasmin，M.Proenant和C.Boucheix。2000年。科学。287：319-321；Miyado，K.，G.Yamada，S.Yamada，H.Hasuwa，Y.Nakamura。首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容2000年。科学。287：321-324)。使用缺乏α6整合素亚基的培养小鼠卵巢的卵子，我们发现与野生型或杂合子对照相比，受精率、受精指数和精子结合没有受到损害。此外，使用一种更好地模拟体内受精条件的方法对抗体抑制进行重新检查，显示GoH3单抗没有抑制融合。我们还发现，抗CD9mAb完全阻断了精子与野生型卵子或缺乏α6β1的卵子的融合。基于这些结果，我们得出结论，α6β1整合素不是精卵融合所必需的，我们建议了一个新的模型，在该模型中，CD9单独作用，或与卵蛋白(S)相互作用而不是α6β1，以发挥精卵融合的作用。
Previous results, based on inhibition of fertilization by an anti-alpha 6 integrin mAb (GoH3), suggest that the alpha 6 beta 1 integrin on mouse eggs functions as the receptor for sperm (Almeida, E.A., A.P. Huovila, A.E. Sutherland. L.E. Stephens PG. Calarco, L.M. Shaw A.M. Mercurio, A. Sonnenberg, P. Primakoff, D.G. Myles, and J.M. White. 1995. Cell. 81:1095-1103). Because the egg surface tetraspanin CD9 is essential for gamete fusion (Kaji, K., S. Oda, T. Shikano, T. Ohnuki, Y. Uematsu. J. Sakagami, N. Tada, S. Miyazaki, and A. Kudo. 2000. Nat. Genet. 24:279-282; Le Naour. F.,E. Rubinstein, C. Jasmin, M. Prenant, and C. Boucheix. 2000. Science. 287:319-321; Miyado, Ii., G. Yamada, S. Yamada, H. Hasuwa, Y. Nakamura, F. Ryu Ii. Suzuki, K. Kosai, K. Inoue, A. Ogura, M. Okabe, and E. Mekada. 2000. Science. 287:321-324) and CD9 is known to associate with integrins, recent models of gamete fusion have posited that egg CD9 acts in association with alpha 6 beta 1 in fusion (Chen, M.S., K.S. Tung, S.A. Coonrod, Y. Takahashi, D. Bigler, A. Chang, Y. Yamashita, P.W. Kincade, J.C. Herr, and J.M. White. 1999. Proc. Natl. Acad. Sci. USA. 96:11830-11835, Kaji, K., S. Oda, T. Shikano, T. Ohnuki, Y. Uematsu, J. Sakagami, N. Tada, S. Miyazaki, and A. Kudo. 2000. Nat. Genet. 24:279-282; Le Naour, E, E. Rubinstein, C. Jasmin, M. Prenant, and C. Boucheix. 2000. Science. 287:319-321; Miyado, K., G. Yamada, S. Yamada, H. Hasuwa, Y. Nakamura. F. Ryu, K. Suzuki, K. Kosai, K. Inoue, A. Ogura, M. Okabe, and E. Mekada. 2000. Science. 287:321-324). Using eggs from cultured ovaries of mice lacking the alpha 6 integrin subunit, we found that the fertilization rate, fertilization index, and sperm binding were not impaired compared with wild-type or heterozygous controls. Furthermore, a reexamination of antibody inhibition, using an assay that better simulates in vivo fertilization conditions, revealed no inhibition of fusion by the GoH3 mAb. We also found that an anti-CD9 mAb completely blocks sperm fusion with either wild-type eggs or eggs lacking alpha 6 beta 1. Based on these results, we conclude that the alpha 6 beta 1 integrin is not essential for sperm-egg fusion, and we suggest a new model in which CD9 acts by itself, or interacts with egg protein(s) other than alpha 6 beta 1,to function in sperm-egg fusion.