The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse.
gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are ligand-gated chloride channels that exist in numerous distinct subunit combinations. At postsynaptic membrane specializations, different GABA(A)R isoforms colocalize with the tubulin-binding protein gephyrin. However, direct interactions of GABA(A)R subunits with gephyrin have not been reported. Recently, the GABA(A)R-associated protein GABARAP was found to bind to the gamma2 subunit of GABA(A)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 GABA(A)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.
Kneussel
M
M
Departments of Neurochemistry and Neuroanatomy, Max Planck Institute for Brain Research, Deutschordenstrasse 46, D-60528 Frankfurt/Main, Germany.
Haverkamp
S
S
Fuhrmann
J C
JC
Wang
H
H
Wässle
H
H
Olsen
R W
RW
Betz
H
H
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007448:Invertebrates / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D013569:Synapses / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018118:Chloride Channels; D019941:Cyclin-Dependent Kinase Inhibitor p16; C116741:GABARAP protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; C073441:gephyrin