Regulation of intracellular glycine as an organic osmolyte in early preimplantation mouse embryos

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Abstract
GLYT1, a glycine transporter belonging to the neurotransmitter transporter family, has recently been identified as a novel cell volume-regulatory mechanism in the earliest stages of the mouse preimplantation embryo. It apparently acts by regulating the steady-state intracellular concentration of glycine, which functions as an organic osmolyte in embryos, to balance external osmolarity and thus maintain cell volume. GLYT1 in embryos was the first mammalian organic osmolyte transporter identified that appears to function in cell volume control under conditions of normal osmolarity, rather than being a response to the stress of chronic hypertonicity. Its maximal rate of transport was shown to be regulated by osmolarity. However, it was not known whether this osmotic regulation of the rate of glycine transport is sufficient to account for the observed control of steady-state intracellular glycine levels as a function of osmolarity in embryos. Here, we show that the intracellular accumulation of glycine in embryos is a direct function of the rate of glycine uptake via GLYT1. In addition, we have shown that the rate of efflux, likely via the volume-regulated anion and organic osmolyte channel in embryos, is also under osmotic regulation and contributes substantially to the control of steady-state glycine concentrations. Together, control of both the rate of uptake and rate of efflux of glycine underlies the mechanism of osmotic regulation of the steady-state concentration of glycine and hence cell volume in early embryos.