Kim Taewan, Oh Jungsu, Woo Jong-Min, Choi Eunyoung, Im Sin Hyeog, Yoo Yung Joon, Kim Do Han, Nishimura Hitoshi, Cho Chunghee
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Biol Reprod. 2006 Apr;74(4):744-50. doi: 10.1095/biolreprod.105.048892. Epub 2006 Jan 11.
A number of a disintegrin and metalloprotease (ADAM) family members are expressed in mammalian male reproductive organs such as testis and epididymis. These reproductive ADAMs are divided phylogenically into three major groups: ADAMs 1, 4, 6, 20, 21, 24, 25, 26, 29, 30, and 34 (the first group); ADAMs 2, 3, 5, 27, and 32 (the second group); and ADAMs 7 and 28 (the third group). Previous mouse knockout studies indicate that ADAM1, ADAM2, and ADAM3 have intricate expressional relationships, playing critical roles in fertilization. In the present study, we analyzed processing, biochemical characteristics, localization, and expressional relationship of the previously-unexplored, second-group ADAMs (ADAM5, ADAM27, and ADAM32). We found that all of the three ADAMs are made as precursors in the testis and processed during epididymal maturation, and that ADAM5 and ADAM32, but not ADAM27, are located on the sperm surface. Using sperm from Adam2(-/-) and Adam3(-/-) mice, we found that, among the three ADAMs, the level of ADAM5 is modestly and severely reduced in Adam3 and Adam2 knockout sperm, respectively. Further, we analyzed ADAM7, an epididymis-derived sperm surface ADAM from the separate phylogenetic group, in the knockout sperm. We found that the level of ADAM7 is also significantly reduced in both Adam2 and Adam3-null sperm. Taken together, our results suggest a novel expressional relationship of ADAM5 and ADAM7 with ADAM2 and ADAM3, which play critical roles in fertilization.
许多解聚素和金属蛋白酶(ADAM)家族成员在哺乳动物雄性生殖器官如睾丸和附睾中表达。这些生殖相关的ADAM在系统发育上分为三大类:ADAM 1、4、6、20、21、24、25、26、29、30和34(第一组);ADAM 2、3、5、27和32(第二组);以及ADAM 7和28(第三组)。先前的小鼠基因敲除研究表明,ADAM1、ADAM2和ADAM3具有复杂的表达关系,在受精过程中发挥关键作用。在本研究中,我们分析了此前未被探索的第二组ADAM(ADAM5、ADAM27和ADAM32)的加工过程、生化特性、定位及表达关系。我们发现这三种ADAM在睾丸中均以前体形式产生,并在附睾成熟过程中进行加工,且ADAM5和ADAM32位于精子表面,而ADAM27不在。利用Adam2(-/-)和Adam3(-/-)小鼠的精子,我们发现,在这三种ADAM中,ADAM5的水平在Adam3基因敲除精子中适度降低,在Adam2基因敲除精子中严重降低。此外,我们在基因敲除精子中分析了ADAM7,它是来自另一个系统发育组的附睾来源的精子表面ADAM。我们发现ADAM7的水平在Adam2和Adam3基因敲除的精子中也显著降低。综上所述,我们的结果提示了ADAM5和ADAM7与在受精中起关键作用的ADAM2和ADAM3之间存在一种新的表达关系。