The sperm-associated antigen 6 interactome and its role in spermatogenesis

Mammalian SPAG6, the orthologue of Chlamydomonas reinhardtii PF16, is a component of the central apparatus of the ‘9 + 2’ axoneme that controls ciliary/flagellar motility, including sperm motility. Recent studies revealed that SPAG6 has functions beyond its role in the central apparatus. Hence, we r...

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Published in:	Reproduction (Cambridge, England) Vol. 158; no. 2; pp. 181 - 197
Main Authors:	Liu, Yunhao, Zhang, Ling, Li, Wei, Huang, Qian, Yuan, Shuo, Li, Yuhong, Liu, Junpin, Zhang, Shiyang, Pin, Guanglun, Song, Shizhen, Ray, Pierre F, Arnoult, Christophe, Cho, Chunghee, Garcia-Reyes, Balbina, Knippschild, Uwe, Strauss, Jerome F, Zhang, Zhibing
Format:	Journal Article
Language:	English
Published:	England Bioscientifica Ltd 01-08-2019
Subjects:	Acrosome - metabolism Animals CHO Cells Cricetulus Infertility, Male - etiology Infertility, Male - metabolism Infertility, Male - pathology Male Mice, Knockout Microtubule Proteins - metabolism Spermatogenesis Spermatozoa - metabolism Spermatozoa - ultrastructure Testis - metabolism Vesicular Transport Proteins - metabolism
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Summary:	Mammalian SPAG6, the orthologue of Chlamydomonas reinhardtii PF16, is a component of the central apparatus of the ‘9 + 2’ axoneme that controls ciliary/flagellar motility, including sperm motility. Recent studies revealed that SPAG6 has functions beyond its role in the central apparatus. Hence, we reexamined the role of SPAG6 in male fertility. In wild-type mice, SPAG6 was present in cytoplasmic vesicles in spermatocytes, the acrosome of round and elongating spermatids and the manchette of elongating spermatids. Spag6-deficient testes showed abnormal spermatogenesis, with abnormalities in male germ cell morphology consistent with the multi-compartment pattern of SPAG6 localization. The armadillo repeat domain of mouse SPAG6 was used as a bait in a yeast two-hybrid screen, and several proteins with diverse functions appeared multiple times, including Snapin, SPINK2 and COPS5. Snapin has a similar localization to SPAG6 in male germ cells, and SPINK2, a key protein in acrosome biogenesis, was dramatically reduced in Spag6-deficient mice which have defective acrosomes. SPAG16L, another SPAG6-binding partner, lost its localization to the manchette in Spag6-deficient mice. Our findings demonstrate that SPAG6 is a multi-functional protein that not only regulates sperm motility, but also plays roles in spermatogenesis in multiple cellular compartments involving multiple protein partners.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contribute equally in this study.
ISSN:	1470-1626 1741-7899
DOI:	10.1530/REP-18-0522