Abstract
Fertilization is essential for species survival. Although Izumo1 and Juno are critical for initial interaction between gametes, additional molecules necessary for sperm:egg fusion on both the sperm and the oocyte remain to be defined. Here, we show that phosphatidylserine (PtdSer) is exposed on the head region of viable and motile sperm, with PtdSer exposure progressively increasing during sperm transit through the epididymis. Functionally, masking phosphatidylserine on sperm via three different approaches inhibits fertilization. On the oocyte, phosphatidylserine recognition receptors BAI1, CD36, Tim-4, and Mer-TK contribute to fertilization. Further, oocytes lacking the cytoplasmic ELMO1, or functional disruption of RAC1 (both of which signal downstream of BAI1/BAI3), also affect sperm entry into oocytes. Intriguingly, mammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts. Collectively, these data identify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players in sperm:egg fusion.
Highlights
IntroductionMammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts
PtdSer can be transiently exposed on viable cells in certain conditions, and we further investigated the relevance of PtdSer exposure on the sperm
When we examined the expression of genes linked to the sperm:egg fusion in myoblasts, we found that oocytes and myoblasts both expressed the membrane proteins CD9, CD36, BAI1, and BAI3, as well as cytoplasmic ELMO2, and RAC1 (Fig. 4a)[8,25,49,56,57,58,59], whereas Juno expression was not detected in myoblasts (Fig. 4b)
Summary
Mammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts. These data identify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players in sperm:egg fusion. It has been suggested that other players on both sperm and the oocyte likely contribute toward gamete fusion (after the Izumo1:Juno interaction)[1,2]. The signaling pathway ELMO1/RAC1, downstream of the PtdSer receptors BAI1/3, participates in this event. This pathway is conserved in the fusion of sperm with myoblasts. Our results shed light into the molecular mechanism of sperm:egg fusion
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