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We investigated the ubiquitin-like modification of GABA(A) receptor-associated protein (GABARAP) and its function. A fusion protein of GABARAP with v5 in the N terminus and myc in the C terminus was expressed in rat cultured hippocampal neurons and PC12 cells. Western blotting with antibodies to v5 and myc revealed that the C terminus of GABARAP was cleaved off. Cleavage was blocked by mutating the C-terminal Gly116 to Ala, suggesting that G116 is required for the processing. Unlike ubiquitin, GABARAP was not incorporated covalently into higher-molecular-weight protein complexes. Nor was GABARAP degraded by ubiquitinylation through the proteasome, although GABARAP formed noncovalent dimers. Immunofluorescent confocal microscopy demonstrated that recombinantly expressed GABARAP was diffusely localized in PC12 cells. However, prevention of C-terminal processing in the mutant GABARAP(G116A) resulted in redistribution to the Golgi. In neurons, punctate cytoplasmic staining of GABARAP was seen in soma and processes, whereas GABARAP(G116A) was limited to soma. Compared with wild-type GABARAP, the colocalization and interaction of GABARAP(G116A) with GABA(A) receptors were significantly reduced, resulting in a reduction in expression of receptors in the plasma membrane. When alpha1beta2gamma2S-containing GABA(A) receptors were expressed in oocytes, the increased surface expression of GABA(A) receptors, as shown by increased GABA currents and surface-accessible GABA(A) receptor subunit polypeptides resulting from GABARAP coexpression, was prevented by mutation G116A. In addition, the distribution of NSF (N-ethylmaleimide-sensitive factor) was affected in GABARAP(G116A)-expressing neurons. These results suggest that glycine 116 is required for C-terminal processing of GABARAP and that processing is essential for the localization of GABARAP and its functions as a trafficking protein.
Bedford,
GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1.
2001, Pubmed
Bedford,
GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1.
2001,
Pubmed Birnir,
Characteristics of GABAA channels in rat dentate gyrus.
1994,
Pubmed Birnir,
GABA concentration sets the conductance of delayed GABAA channels in outside-out patches from rat hippocampal neurons.
2001,
Pubmed Boileau,
Tandem subunits effectively constrain GABAA receptor stoichiometry and recapitulate receptor kinetics but are insensitive to GABAA receptor-associated protein.
2005,
Pubmed Chang,
A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation.
2003,
Pubmed
,
Xenbase Chen,
The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics.
2000,
Pubmed Chen,
GABAA receptor associated proteins: a key factor regulating GABAA receptor function.
2007,
Pubmed Chen,
GABAA receptor-associated protein regulates GABAA receptor cell-surface number in Xenopus laevis oocytes.
2005,
Pubmed
,
Xenbase Coyle,
Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding.
2002,
Pubmed Curmi,
The influence of membrane potential on chloride channels activated by GABA in rat cultured hippocampal neurons.
1993,
Pubmed DeSouza,
Differential palmitoylation directs the AMPA receptor-binding protein ABP to spines or to intracellular clusters.
2002,
Pubmed El-Husseini,
Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering.
2000,
Pubmed Everitt,
Conductance of recombinant GABA (A) channels is increased in cells co-expressing GABA(A) receptor-associated protein.
2004,
Pubmed Fatima-Shad,
A patch-clamp study of GABA- and strychnine-sensitive glycine-activated currents in post-natal tissue-cultured hippocampal neurons.
1992,
Pubmed Hemelaar,
A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L.
2003,
Pubmed Hochstrasser,
Biochemistry. All in the ubiquitin family.
2000,
Pubmed Ichimura,
A ubiquitin-like system mediates protein lipidation.
2000,
Pubmed Jin,
Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity.
2006,
Pubmed Kabeya,
LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation.
2004,
Pubmed Kabeya,
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
2000,
Pubmed Keller,
The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ.
2004,
Pubmed Keller,
Multicolour imaging of post-Golgi sorting and trafficking in live cells.
2001,
Pubmed Kittler,
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.
2001,
Pubmed Kittler,
Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking.
2004,
Pubmed Kneussel,
The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse.
2000,
Pubmed Knight,
The X-ray crystal structure and putative ligand-derived peptide binding properties of gamma-aminobutyric acid receptor type A receptor-associated protein.
2002,
Pubmed Komatsu,
The C-terminal region of an Apg7p/Cvt2p is required for homodimerization and is essential for its E1 activity and E1-E2 complex formation.
2001,
Pubmed Legesse-Miller,
Isolation and characterization of a novel low molecular weight protein involved in intra-Golgi traffic.
1998,
Pubmed Leil,
GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neurons.
2004,
Pubmed Macdonald,
GABAA receptor channels.
1994,
Pubmed Mansuy,
GEC1, a protein related to GABARAP, interacts with tubulin and GABA(A) receptor.
2004,
Pubmed Muller,
Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion.
2002,
Pubmed Müller,
SUMO, ubiquitin's mysterious cousin.
2001,
Pubmed Nymann-Andersen,
Biochemical identification of the binding domain in the GABA(A) receptor-associated protein (GABARAP) mediating dimer formation.
2002,
Pubmed O'Sullivan,
GABARAP is not essential for GABA receptor targeting to the synapse.
2005,
Pubmed Raju,
Autoimmunity to GABAA-receptor-associated protein in stiff-person syndrome.
2006,
Pubmed Rothman,
Intracellular membrane fusion.
1994,
Pubmed Sagiv,
GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28.
2000,
Pubmed Scherz-Shouval,
The COOH terminus of GATE-16, an intra-Golgi transport modulator, is cleaved by the human cysteine protease HsApg4A.
2003,
Pubmed Stangler,
Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biolgoical funcrion and its regulation.
2002,
Pubmed Tanida,
HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates.
2004,
Pubmed Tanida,
Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p.
2002,
Pubmed Tanida,
The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3.
2001,
Pubmed Tanida,
GATE-16 and GABARAP are authentic modifiers mediated by Apg7 and Apg3.
2003,
Pubmed Wallner,
Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans.
2003,
Pubmed
,
Xenbase Wang,
Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction.
2000,
Pubmed Wang,
GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton.
1999,
Pubmed Yamazaki-Sato,
The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
2003,
Pubmed
