Abstract
Globozoospermia is a common reproductive disorder that causes male infertility in humans, and the malformation or loss of acrosomes is the prominent feature of this disease. Although the acrosome is thought to be derived from the Golgi apparatus, the detailed molecular mechanisms remain unclear. GM130 is a cis-side localized Golgi matrix protein,whereas the physiological functions of this protein remain elusive. Here we showed that inactivation of GM130-caused male infertility in mouse model. The primary defects were the absence of acrosomes, round sperm heads, and aberrant assembly of the mitochondrial sheath, which comprise the characteristic features of human globozoospermia. Further investigation indicated that loss of GM130 did not affect the secretion of pro-acrosomic vesicles, whereas the vesicles failed to fuse into a single large acrosome vesicle. Co-localization of the adaptor protein complex AP1 and trans-Golgi network (TGN) protein TGN46 was disrupted, suggesting that the malformation of acrosomes is most likely due to the defect in the sorting and coating of Golgi-derived pro-acrosomic vesicles. Thus, the GM130-deficient mouse provides a valuable model for investigating the etiology of human globozoospermia.
Highlights
Spermiogenesis is a fundamental process required for the generation of the mature male gamete with a vesicle-like acrosome, a propelling flagellum, and condensed nucleus, which are all necessary for successful fertilization
We demonstrated that the loss of GM130 did not affect the secretion of pro-acrosomic vesicles from the Golgi apparatus, whereas the vesicles failed to move to the concave region of the spermatid nucleus and fuse into a single large acrosomic granule
GM130−/−mice were appeared grossly normal at birth; only 50% of the mice survived until the adult stage, and the body size was significantly reduced compared with that of the control littermates
Summary
Spermiogenesis is a fundamental process required for the generation of the mature male gamete with a vesicle-like acrosome, a propelling flagellum, and condensed nucleus, which are all necessary for successful fertilization. Our recent study has demonstrated that the autophagy process is required for acrosome biogenesis, and the inactivation of the autophagyassociated gene Atg[7] causes malformation of the acrosome and a round-headed spermatid.[14]. GM130 was first isolated from the Golgi matrix as a structural protein which is localized at the cis-side of the Golgi complex.[15,16] As a member of the golgin family, the function of GM130 has been investigated using in vitro systems.[16,17] Together with p115, giantin, and GRASP65, GM130 is thought to play roles in ER-derived vesicle tethering and fusion at the Golgi membrane, thereby maintaining the Golgi structure integrity.[18,19,20,21] Emerging evidence has indicated that GM130 has essential roles in the control of cell polarity, cell division, and cell migration.[22,23,24,25] A recent study has demonstrated that GM130 is involved in the Golgi-derived spindle assembly via TPX2 activation and microtubule capture.[26]. The loss of GM130 probably causes the defect of sorting and coating of Received 02.6.16; revised 17.10.16; accepted 27.10.16; Edited by M Agostini
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