Fig 7. Schematic of GGPP-mediated protein geranylgeranylation involving in the regulation of primary-secondary follicle transition via remodeling oocyte-granulosa cell communication.

Cholesterol was biosynthesized from farnesyl diphosphate (FPP), a metabolic intermediate of the mevalonate pathway. FPP could be catalyzed into another metabolite, geranylgeranyl diphosphate (GGPP), by geranylgeranyl diphosphate synthase (GGPPS). GGPP then was used for the geranylgeranylation and activation of Rho GTPase and Rab GTPase. The activated Rho GTPase was responsible for the localization of cell junction proteins in the oocyte membrane to maintain physical connection between oocyte and granulosa cells. The activated Rab GTPase might account for the secretion of oocyte materials such as Gdf9. The two processes were probably important for the proliferation of granulosa cells from one layer to multiple layers and ultimately promote the primary-secondary follicle transition. The pathway in the box might mainly occur in granulosa cells. Dashed arrows depicted possible mechanism of GGPP-regulated small GTPase on oocyte-granulosa cell communication.