Adenosine-to-inosine RNA editing affects trafficking of the gamma-aminobutyric acid type A (GABA(A)) receptor.

ABSTRACT: Recoding by adenosine-to-inosine RNA editing plays an important role in diversifying proteins involved in neurotransmission. We have previously shown that the Gabra-3 transcript, coding for the ?3 subunit of the GABA(A) receptor is edited in mouse, causing an isoleucine to methionine (I/M) change. Here we show that this editing event is evolutionarily conserved from human to chicken. Analyzing recombinant GABA(A) receptor subunits expressed in HEK293 cells, our results suggest that editing at the I/M site in ?3 has functional consequences on receptor expression. We demonstrate that I/M editing reduces the cell surface and the total number of ?3 subunits. The reduction in cell surface levels is independent of the subunit combination as it is observed for ?3 in combination with either the ?2 or the ?3 subunit. Further, an amino acid substitution at the corresponding I/M site in the ?1 subunit has a similar effect on cell surface presentation, indicating the importance of this site for receptor trafficking. We show that the I/M editing during brain development is inversely related to the ?3 protein abundance. Our results suggest that editing controls trafficking of ?3-containing receptors and may therefore facilitate the switch of subunit compositions during development as well as the subcellular distribution of ? subunits in the adult brain.

SUBMITTER: Daniel C 

PROVIDER: S-EPMC3023500 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature