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A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology: Assembly into heteromeric receptor complexes

Item Type:Article
Title:A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology: Assembly into heteromeric receptor complexes
Creators Name:Oertel, J. and Villmann, C. and Kettenmann, H. and Kirchhoff, F. and Becker, C.M.
Abstract:The inhibitory glycine receptor is a ligand-gated ion channel with a pentameric assembly from ligand binding a and structural ss subunits. In addition to a subunit gene variants (a1-a4) and developmental alterations in subunit composition of the receptor protein complex, alternative splicing of a subunits has been found to contribute to glycine receptor heterogeneity. Here, we describe a novel splice variant of the glycine receptor ss subunit from mouse CNS, prevailing in macroglial cells, predominantly in astrocytes and extraneural tissues. As predicted by its cDNA sequence, the novel subunit ss7 lacks amino acid positions 252-301 encoded by exon 7 of the Glrb gene. Transcripts and antigen of ss7 were detected in cerebral cortex, liver and heart. Lack of exon 7 results in a profoundly altered prediction of trans-membrane topology as ss7 lacks TM1 and TM2 present in the full length variant. Despite these topological alterations, in vitro studies showed that the ss7 polypeptide integrates into the plasma membrane, forming receptor complexes with the a1 subunit and gephyrin. Our data demonstrate that a topology deviating from the classical four transmembrane fold is compatible with formation of glycine receptor protein complexes. However, co-expression of a1 with ss7 subunits did not change glycine receptor channel properties. Rather, the high level of expression in non-neuronal cells having intimate contact with synaptic regions may account for a yet unknown function of this splice variant ss7 in glycinergic neurotransmission.
Keywords:Astrocytes, Base Sequence, Brain, Cell Line, Cerebral Cortex, DNA Primers, Complementary DNA, Exons, Heart, Kidney, Liver, RNA, Glycine Receptors, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Deletion, Genetic Transcription, Transfection, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:282
Number:5
Page Range:2798-2807
Date:2 February 2007
Official Publication:https://doi.org/10.1074/jbc.M608941200
PubMed:View item in PubMed

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