Open AccessThe γ-aminobutyric acid type A receptor (GABA A R)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse
Author(s) -
Matthias Kneussel,
Silke Haverkamp,
Jens C. Fuhrmann,
Hongbing Wang,
Heinz Wässle,
Richard W. Olsen,
Heinrich Betz
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.15.8594
Subject(s) - gephyrin , microbiology and biotechnology , postsynaptic potential , protein subunit , glycine receptor , biology , colocalization , postsynaptic density , receptor , gabaa receptor , chemistry , biochemistry , amino acid , glycine , gene
γ-Aminobutyric acid type A receptors (GABAA Rs) are ligand-gated chloride channels that exist in numerous distinct subunit combinations. At postsynaptic membrane specializations, different GABAA R isoforms colocalize with the tubulin-binding protein gephyrin. However, direct interactions of GABAA R subunits with gephyrin have not been reported. Recently, the GABAA R-associated protein GABARAP was found to bind to the γ2 subunit of GABAA Rs. Here we show that GABARAP interacts with gephyrin in both biochemical assays and transfected cells. Confocal analysis of neurons derived from wild-type and gephyrin-knockout mice revealed that GABARAP is highly enriched in intracellular compartments, but not at gephyrin-positive postsynaptic membrane specializations. Our data indicate that GABARAP–gephyrin interactions are not important for postsynaptic GABAA R anchoring but may be implicated in receptor sorting and/or targeting mechanisms. Consistent with this idea, a close homolog of GABARAP, p16, has been found to function as a late-acting intra-Golgi transport factor.