Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish

The glycine receptor is a ligand-gated anion channel protein, providing inh ibitory drive within the nervous system. We report here the isolation and f unctional characterization of a novel alpha subunit (alpha Z1) of the glyci ne receptor from adult zebrafish (Danio rerio) brain. The predicted amino a cid sequence is 86%, 81% and 77% identical to mammalian isoforms alpha 1, a lpha 3 and alpha 2, respectively. alpha Z1 exhibits many of the molecular f eatures of mammalian alpha 1, but the sequence patterns in the M4 and C-ter minal domains are more similar to alpha 2/alpha 3. Phylogenetic analysis in dicates that alpha Z1 is more closely related to the mammalian alpha l subu nits, being positioned, however, on a distinct branch. The alpha Z1 messeng er RNA is 9.5 kb, similar to that described previously for alpha 1 messenge r RNAs. When expressed in Xenopus oocytes or a human cell line (BOSC 23), a lpha Z1 forms a homomeric receptor which is activated by glycine and antago nized by strychnine. This receptor demonstrates unexpectedly high sensitivi ty to taurine and can also be activated by GABA. These results are consistent with physiological findings in lamprey and gol dfish, and they suggest that this teleost fish glycine receptor displays a lower selectivity to neurotransmitters than that reported for glycine mamma lian receptors. (C) 1999 IBRO. Published by Elsevier Science Ltd.