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  • The EMBO Journal (1999) 18, 4711 - 4721
  • doi:10.1093/emboj/18.17.4711

Molecular determinants of glycine receptor subunit assembly

Nathalie Griffon1,2, Cora Büttner3, Annette Nicke3, Jochen Kuhse1,4, Günther Schmalzing3 and Heinrich Betz1

  1. Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, D-60528 Frankfurt am Main, Germany
  2. Present address: Unité de Neurobiologie et Pharmacologie Moleculaire, INSERM U 109, Centre Paul Broca 2ter, rue d'Alesia, 75014 Paris, France
  3. Department of Pharmacology, Biocenter of the Johann Wolfgang Goethe-University, Marie-Curie-Strasse 9, D-60439 Frankfurt am Main, Germany
  4. Present address: Department of Anatomy and Cellular Neurobiology, University of Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany

Correspondence to:

Heinrich Betz, E-mail: neurochemie@mpih-frankfurt.mpg.de

Received 4 May 1999; Accepted 6 July 1999; Revised 6 July 1999

The inhibitory glycine receptor (GlyR) is a pentameric transmembrane protein composed of homologous alpha and beta subunits. Single expression of alpha subunits generates functional homo-oligomeric GlyRs, whereas the beta subunit requires a co-expressed alpha subunit to assemble into hetero-oligomeric channels of invariant stoichiometry (alpha3beta2). Here, we identified eight amino acid residues within the N-terminal region of the alpha1 subunit that are required for the formation of homo-oligomeric GlyR channels. We show that oligomerization and N-glycosylationq of the alpha1 subunit are required for transit from the endoplasmic reticulum to the Golgi apparatus and later compartments, and that addition of simple carbohydrate side chains occurs prior to GlyR subunit assembly. Our data are consistent with both intersubunit surface and conformational differences determining the different assembly behaviour of GlyR alpha and beta subunits.

  • Keywords:

    • glycine receptor,
    • N-glycosylation,
    • oligomerization,
    • subunit stoichiometry