Vitamin K2-Dependent GGCX and MGP Are Required for Homeostatic Calcium Regulation of Sperm Maturation

• Main Authors: He Ma, Bao Li Zhang, Bao Ying Liu, Shuo Shi, Da Yuan Gao, Tian Cheng Zhang, Hui Juan Shi, Zhen Li, Winnie Waichi Shum
• Format: Article
• Language: English
• Published: Elsevier 2019-04-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004219300963

Summary: A low-calcium microenvironment is essential for spermatozoa to mature in the epididymis; however, it remains unclear how dysregulation of epididymal luminal calcium is associated with male infertility. Using a warfarin-induced vitamin K2 deficiency rat model, we found that vitamin-K-dependent γ-glutamyl carboxylase (GGCX) and matrix Gla protein (MGP) were essential in extracellular calcium signaling of the intercellular communication required for epididymal sperm maturation. We found that GGCX and MGP co-localized in the vesicular structures of epididymal cells and spermatozoa. Calcium-regulated MGP binds to proteins in a biphasic manner; sub-millimolar calcium enhances, whereas excessive calcium inhibits, the binding. Bioinformatic analysis of the calcium-dependent MGP-bound proteome revealed that vesicle-mediated transport and membrane trafficking underlie the intercellular communication networks. We also identified an SNP mutation, rs699664, in the GGCX gene of infertile men with asthenozoospermia. Overall, we revealed that the GGCX-MGP system is integrated with the intercellular calcium signaling to promote sperm maturation. : Cell Biology; Developmental Biology; Specialized Functions of Cells Subject Areas: Cell Biology, Developmental Biology, Specialized Functions of Cells