Expression and Relationship of Male Reproductive ADAMs in Mouse1

Abstract

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.

Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer

“…Similarly, the ADAM28s isoform contains a novel translated sequence of 56 nucleotides in intron 14 that results in a truncated protein with a 17 amino acid short cysteine-rich domain, remarkably similar to the D14 0 isoform. These findings suggest a similar evolutionary origin (Fourie et al, 2003) (Kim et al, 2006) and highly conserved mechanism of splicing among different ADAM family members.…”

Lack of Tyrosylprotein Sulfotransferase-2 Activity Results in Altered Sperm-Egg Interactions and Loss of ADAM3 and ADAM6 in Epididymal Sperm

“…Misfolded proteins that progress to more distal parts of the secretory pathway can be retrotranslocated to the ER and subjected to ER-associated degradation. An additional layer of the quality control pathway also occurring past the ER is formation of higher order oligomers of certain proteins in the ER- (40,53), with much of the ADAM3 loss occurring during protein transit from the trans-Golgi to the cell surface, such that little or no ADAM3 was detected on the surfaces of Adam2-null cells (54,55). Adam3-null sperm also have reduced amounts of several ADAMs (30,40,53).…”

“…An additional layer of the quality control pathway also occurring past the ER is formation of higher order oligomers of certain proteins in the ER- (40,53), with much of the ADAM3 loss occurring during protein transit from the trans-Golgi to the cell surface, such that little or no ADAM3 was detected on the surfaces of Adam2-null cells (54,55). Adam3-null sperm also have reduced amounts of several ADAMs (30,40,53). Protein folding also is important for ADAM stability because Clgn-null sperm lack detectable ADAM1B, ADAM2, and ADAM3; these proteins are lost posttranslationally, probably due to aberrant protein folding due to the Clgn deficiency (44,45).…”

More Than a Simple Lock and Key Mechanism: Unraveling the Intricacies of Sperm-Zona Pellucida Binding

“…Angiotensin-converting enzyme (ACE) Mouse Rat Horse Human  Testis-specific form is found within developing spermatids and mature sperm  ACE KO mice are infertile due to defective transport in the oviducts as well as decreased zona pellucida binding  Play significant role in redistribution of ADAM3 to the sperm surface (Esther, et al, 1996, Foresta, et al, 1991, Kohn, et al, 1995, Langford, et al, 1993, Sibony, et al, 1993 A disintegrin and metalloproteinase (ADAMs) Mouse Rat Pig Human  Family of transmembrane proteins that have varying roles in maturation of spermatozoa  ADAM3 has important role in zona pellucida binding  ADAM2 KO mice show strong suppression of zona pellucida binding and difficulty in moving through female reproductive tract, due to absence of ADAM3 in these mice  ADAM1a KO mice are fertile, but show decreased levels of ADAM3 on the sperm surface  ADAM1b KO mice are fertile , Kim, et al, 2006a, Kim, et al, 2006b, Nishimura, et al, 2007, Yamaguchi, et al, 2009 protein that may facilitate sperm-zona pellucida binding by adhering to mannose-containing zona pellucida oligosaccharides (Cornwall, et al, 1991, Tulsiani, et al, 1993, Tulsiani, et al, 1989, Yoshida-Komiya, et al, 1999, , Hess, et al, 1996, Tantibhedhyangkul, et al, 2002, Weerachatyanukul, et al, 2003 Calmegin (CLGN)/Calnexin/Calspernin (CALR3)…”