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THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 3, pp. 2031–2040, January 21, 2011 ? 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. Adenosine-to-Inosine RNA Editing Affects Trafficking of the ? *□S -Aminobutyric Acid Type A (GABAA) Receptor Received for publication, April 16, 2010, and in revised form, October 28, 2010 Published, JBC Papers in Press, October 28, 2010, DOI 10.1074/jbc.M110.130096 Chammiran Daniel, Helene Wahlstedt, Johan Ohlson, Petra Bjo¨rk, and Marie O¨ hman1 From the Department of Molecular Biology and Functional Genomics, Stockholm University, SE-10691 Stockholm, Sweden Recoding by adenosine-to-inosine RNA editing plays an im- coupled receptor and thereby creating diverse isoforms of portant role in diversifying proteins involved in neurotrans- proteins essential for balanced neuronal kinetics (reviewed in mission. We have previously shown that the Gabra-3 tran- Ref. 1). ? script, coding for the 3 subunit of the GABAA receptor is One of the most well studied substrates for editing in the edited in mouse, causing an isoleucine to methionine (I/M) brain is the transcript coding for the AMPA glutamate recep- change. Here we show that this editing event is evolutionarily tor (GluA). AMPA receptors consist of four subunits (GluA1– conserved from human to chicken. Analyzing recombinant GluA4) in different combinations. Changing a codon for glu- GABAA receptor subunits expressed in HEK293 cells, our re- tamine to arginine in GluA2 is essential to the organism and ? sults suggest that editing at the I/M site in 3 has functional required for a normal brain development (2, 3). consequences on receptor expression. We demonstrate that We have previously