Asymmetric contribution of α and β subunits to the activation of αβ heteromeric glycine receptors

This study investigated the role of beta subunits in the activation of alphabeta heteromeric glycine receptor (GlyR) chloride channels recombinantly expressed in HEK293 cells. The approach involved incorporating mutations into corresponding positions in alpha and beta subunits and comparing their effects on receptor function. Although cysteine-substitution mutations to residues in the N-terminal half of the alpha subunit M2-M3 loop dramatically impaired the gating efficacy, the same mutations exerted little effect when incorporated into corresponding positions of the beta subunit. Furthermore, although the alpha subunit M2-M3 loop cysteines were modified by a cysteine-specific reagent, the corresponding beta subunit cysteines showed no evidence of reactivity. These observations suggest structural or functional differences between alpha and beta subunit M2-M3 loops. In addition, a threonine-->leucine mutation at the 9' position in the beta 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 beta subunit is involved in receptor gating. In conclusion, this study demonstrates that beta subunits contribute to the activation of the GlyR, but that their involvement in this process is significantly different to that of the alpha subunit.

Editorial

The year 2003 marks the 30th anniversary of The Australian Journal of Indigenous Education (AJIE) and coincides with the re-launching of the journal as a peer reviewed research journal.Beginning life in 1973 as The Aboriginal Child at School, AJIE has played a vital role in raising awareness of educational issues for Aboriginal and Torres Strait Islander peoples; fostering debate amongst researchers, government representatives and community groups; and sharing stories of success between both Indigenous and non- Indigenous practitioners positioned in the broad area of Aboriginal and Torres Strait Islander education. The dialogue which has taken place in AJIE over the past 30 years maps out the social, political and cultural history of Indigenous education in Australia, and draws attention to the shifting paradigms,problems and practical outcomes.