The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors.
GABA(A) receptors the major sites of fast synaptic inhibition in the brain are composed predominately of alpha, beta, and gamma2 subunits. The receptor gamma2 subunit interacts with a 17-kDa microtubule associated protein GABARAP, but the significance of this interaction remains unknown. Here we demonstrate that GABARAP, which immunoprecipitates with GABA(A) receptors, is not found at significant levels within inhibitory synapses, but is enriched within the Golgi apparatus and postsynaptic cisternae. We also demonstrate that GABARAP binds directly to N-ethylmaleimide-sensitive factor (NSF), a protein critical for intracellular membrane trafficking events. NSF and GABARAP complexes could be detected in neurons and these two proteins also colocalize within intracellular membrane compartments. Together our observations suggest that GABARAP may play a role in intracellular GABA(A) receptor transport but not synaptic anchoring, via its ability to interact with NSF. GABARAP may therefore have an important role in the production of GABAergic synapses.
Kittler
J T
JT
Medical Research Council Laboratory of Molecular Cell Biology, University College London (UCL), London, WC1E 6BT, United Kingdom.
Rostaing
P
P
Schiavo
G
G
Fritschy
J M
JM
Olsen
R
R
Triller
A
A
Moss
S J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001369:Axons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D014162:Transfection; D033921:Vesicular Transport Proteins
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C116741:GABARAP protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011963:Receptors, GABA-A; D033921:Vesicular Transport Proteins; C073441:gephyrin; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat