These authors contributed equally to this study.
Asymmetric contribution of α and β subunits to the activation of αβ heteromeric glycine receptors
Version of Record online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 2, pages 498–507, July 2003
How to Cite
Shan, Q., Nevin, S. T., Haddrill, J. L. and Lynch, J. W. (2003), Asymmetric contribution of α and β subunits to the activation of αβ heteromeric glycine receptors. Journal of Neurochemistry, 86: 498–507. doi: 10.1046/j.1471-4159.2003.01872.x
- Issue online: 4 FEB 2004
- Version of Record online: 4 FEB 2004
- Received October 21, 2002; revised manuscript received March 17, 2003; accepted April 25, 2003.
- allosteric interactions;
- glycine receptor chloride channel;
- receptor structure and function;
- substituted cysteine accessibility method
This study investigated the role of β subunits in the activation of αβ heteromeric glycine receptor (GlyR) chloride channels recombinantly expressed in HEK293 cells. The approach involved incorporating mutations into corresponding positions in α and β subunits and comparing their effects on receptor function. Although cysteine-substitution mutations to residues in the N-terminal half of the α subunit M2–M3 loop dramatically impaired the gating efficacy, the same mutations exerted little effect when incorporated into corresponding positions of the β subunit. Furthermore, although the α subunit M2–M3 loop cysteines were modified by a cysteine-specific reagent, the corresponding β subunit cysteines showed no evidence of reactivity. These observations suggest structural or functional differences between α and β subunit M2–M3 loops. In addition, a threonineleucine mutation at the 9′ position in the β subunit M2 pore-lining domain dramatically increased the glycine sensitivity. By analogy with the effects of the same mutation in other ligand-gated ion channels, it was concluded that the mutation affected the GlyR activation mechanism. This supports the idea that the GlyR β subunit is involved in receptor gating. In conclusion, this study demonstrates that β subunits contribute to the activation of the GlyR, but that their involvement in this process is significantly different to that of the α subunit.