The Glycine Neurotransmitter Transporter GLYT1 Is an Organic Osmolyte Transporter Regulating Cell Volume in Cleavage-Stage Embryos

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 24; pp. 13982 - 13987
• Main Authors: Steeves, Candace L., Hammer, Mary-Anne, Walker, Glenn B., Rae, Duncan, Stewart, Nicolas A., Baltz, Jay M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 25.11.2003; National Acad Sciences
• Subjects: Amino Acid Transport Systems, Neutral - antagonists & inhibitors; Amino Acid Transport Systems, Neutral - metabolism; Animal cells; Animals; Biological Sciences; Biological Transport, Active - drug effects; Blastocyst; Cell lines; Cell Size; Cellular biology; Cleavage Stage, Ovum - cytology; Cleavage Stage, Ovum - drug effects; Cleavage Stage, Ovum - metabolism; Embryos; Female; Glycine - metabolism; Glycine Plasma Membrane Transport Proteins; Inhibitory concentration 50; Kinetics; Mice; Osmoregulation; Piperidines - pharmacology; Pregnancy; Protein synthesis; Stem cells; Totipotent stem cells; Water-Electrolyte Balance; Zygotes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2334537100

Cells subjected to sustained high osmolarity almost universally respond by accumulating compatible organic osmolytes that, in contrast to inorganic ions, are not deleterious even at high intracellular concentrations. Their accumulation from the external environment by known organic osmolyte transporters, such as the four identified in mammals, occurs only slowly in response to sustained high osmolarity, by synthesis of new transporter proteins. Most cells, however, are not subject to high or varying osmolarity, and it is not clear whether organic osmolytes are generally required at normal osmolarities or how they are regulated. The fertilized egg of the mouse is protected in the oviduct from perturbations in osmolarity. However, deleterious effects of osmotic stress were evident in vitro even at normal oviductal osmolarity. Glycine was found to protect development, indicating that early mouse embryos may use glycine as an organic osmolyte at physiological osmolarity. We have now found that GLYT1, a glycine transporter of the neurotransmitter transporter gene family, functions as the organic osmolyte transporter that mediates the osmotically regulated accumulation of glycine and regulates cell volume in early embryos. Furthermore, osmotic stimulation of GLYT1 transport was immediate, without a requirement for protein synthesis, implying regulation different from known organic osmolyte transporters. Thus, GLYT1 appears to have a previously unidentified role as an organic osmolyte transporter that functions in acute organic osmolyte and volume homeostasis near normal osmolarity.