Rab10 regulates cortical granule translocation and ZP2 dynamics for zona pellucida function during oocyte maturation

ABSTRACT Successful fertilization is important for early embryo development and offspring generation. Cortical granules, which are formed in the cytoplasm, are transported to the cortex to avoid polyspermy, which prevents sperm penetration into oocytes. The underlying mechanism is still largely unknown. In this study, we have identified that GTPase Rab10-mediated vesicles play a pivotal role in actin dynamics, which regulate cortical granule transport and ZP2 function in mouse and porcine oocytes. We found that Rab10 accumulated at the mouse and porcine oocyte cortex and modulated the RhoA pathway to control actin dynamics. Disrupting the functions of Rab10 affected myosin Va expression, which impaired cortical granule movement to the cortex, causing an insufficient supply of cortical granule contents and weakened zona pellucida modification. In addition, overexpression of GDP-bound Rab10 led to ZP2 downregulation and accumulation at the cortex, which affected zona pellucida reaction. Taken together, our findings demonstrate that Rab10 regulates the RhoA pathway for actin dynamics and the myosin Va complex for the cortical granule-based cortical reaction, and the Rab10-ZP2 complex contributes to the ZP2 supply that is necessary for the zona pellucida reaction.