Intracellular glycine receptor function facilitates glioma formation in vivo


  • B. Förstera
  • O.D. a Dzaye
  • A. Winkelmann
  • M. Semtner
  • B. Benedetti
  • D.S. Markovic
  • M. Synowitz
  • P. Wend
  • M. Fähling
  • M.P. Junier
  • R. Glass
  • H. Kettenmann
  • J.C. Meier


  • Journal of Cell Science


  • J Cell Sci 127 (Pt 17): 3687-3698


  • The neuronal function of Cys-loop neurotransmitter receptors is established; however, their role in non-neuronal cells is poorly defined. As brain tumors accumulate the neurotransmitter glycine, we studied expression and function of glycine receptors (GlyR) in glioma cells. Human brain tumor biopsies selectively expressed GlyR subunits with nuclear import signal (NLS, {alpha}1 and {alpha}3). The mouse glioma cell line GL261 expressed GlyR {alpha}1, and knock-down of {alpha}1 protein expression impaired self-renewal capacity and tumorigenicity of GL261 glioma cells as evidenced by the neurosphere assay and GL261 cell inoculation in vivo, respectively. We furthermore show that the pronounced tumorigenic effect of GlyR {alpha}1 relies on a new intracellular signaling function that depends on the NLS region in the large cytosolic loop and impacts on GL261 glioma cell gene regulation. Stable expression of GlyR {alpha}1 and {alpha}3 loops rescued self-renewal capacity of GlyR {alpha}1 knock-down cells, which demonstrates their functional equivalence. The new intracellular signaling function identified here goes beyond the well-established role of GlyRs as neuronal ligand-gated ion channels and defines NLS-containing GlyRs as novel potential targets for brain tumor therapies.