Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton.[2]
Moreover, GABARAP has an important function in autophagosome mediated autophagy, since it is crucial for autophagosome formation and sequestration of cytosolic cargo into double-membrane vesicles, leading to subsequent degradation after fusion with lysosomes.[3] In addition, GABARAP can mediate selective autophagy because it binds to so-called autophagic receptors (e.g. p62, NBr1), which bind and recruit specific cargo.
↑Szalai P, Hagen LK, Sætre F, Luhr M, Sponheim M, Øverbye A, Mills IG, Seglen PO, Engedal N (2015). "Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs". Experimental Cell Research. 333 (1): 21–38. doi:10.1016/j.yexcr.2015.02.003. PMID25684710.
↑Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP". FEBS Letters. 518 (1–3): 101–106. doi:10.1016/S0014-5793(02)02655-8. PMID11997026.
↑Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID17353931.
↑Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M (Dec 2000). "Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation". Brain Research. Molecular Brain Research. 85 (1–2): 1–12. doi:10.1016/S0169-328X(00)00218-7. PMID11146101.
↑Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (Mar 2002). "Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors". Journal of Neurochemistry. 80 (5): 815–823. doi:10.1046/j.0022-3042.2002.00762.x. PMID11948245.
↑Coyle JE, Qamar S, Rajashankar KR, Nikolov DB (Jan 2002). "Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding". Neuron. 33 (1): 63–74. doi:10.1016/S0896-6273(01)00558-X. PMID11779480.
Further reading
Kanematsu T, Hirata M (Apr 2002). "[The analysis of protein-protein interaction with special reference to PRIP-1]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 119 (4): 241–6. doi:10.1254/fpj.119.241. PMID11979730.
Paz Y, Elazar Z, Fass D (Aug 2000). "Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p". The Journal of Biological Chemistry. 275 (33): 25445–25450. doi:10.1074/jbc.C000307200. PMID10856287.
Wang H, Olsen RW (Aug 2000). "Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction". Journal of Neurochemistry. 75 (2): 644–655. doi:10.1046/j.1471-4159.2000.0750644.x. PMID10899939.
Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M (Dec 2000). "Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation". Brain Research. Molecular Brain Research. 85 (1–2): 1–12. doi:10.1016/S0169-328X(00)00218-7. PMID11146101.
Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S (Jun 2001). "Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein". Genomics. 74 (3): 408–413. doi:10.1006/geno.2001.6555. PMID11414770.
Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ (Jul 2001). "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". Molecular and Cellular Neurosciences. 18 (1): 13–25. doi:10.1006/mcne.2001.1005. PMID11461150.
Stangler T, Mayr LM, Dingley AJ, Luge C, Willbold D (Oct 2001). "Sequence-specific 1H, 13C and 15N resonance assignments of human GABA receptor associated protein". Journal of Biomolecular NMR. 21 (2): 183–4. doi:10.1023/A:1012416810974. PMID11727985.
Harris R, McAlister MS, Sankar A, Phelan JP, Moss SJ, Keep NH, Driscoll PC (Oct 2001). "Backbone 1H, 13C, and 15N resonance assignments for a 14 kD protein, GABA(A) receptor associated protein (GABARAP)". Journal of Biomolecular NMR. 21 (2): 185–6. doi:10.1023/A:1012473609468. PMID11727986.
Knight D, Harris R, McAlister MS, Phelan JP, Geddes S, Moss SJ, Driscoll PC, Keep NH (Feb 2002). "The X-ray crystal structure and putative ligand-derived peptide binding properties of gamma-aminobutyric acid receptor type A receptor-associated protein". The Journal of Biological Chemistry. 277 (7): 5556–5561. doi:10.1074/jbc.M109753200. PMID11729197.
Coyle JE, Qamar S, Rajashankar KR, Nikolov DB (Jan 2002). "Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding". Neuron. 33 (1): 63–74. doi:10.1016/S0896-6273(01)00558-X. PMID11779480.
Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E (Apr 2002). "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". The Journal of Biological Chemistry. 277 (16): 13739–13744. doi:10.1074/jbc.M200385200. PMID11825910.
Stangler T, Mayr LM, Willbold D (Apr 2002). "Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biolgoical funcrion and its regulation". The Journal of Biological Chemistry. 277 (16): 13363–13366. doi:10.1074/jbc.C200050200. PMID11875056.
Kouno T, Miura K, Kanematsu T, Shirakawa M, Hirata M, Kawano K (Jan 2002). "1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor associated protein". Journal of Biomolecular NMR. 22 (1): 97–98. doi:10.1023/A:1013884402033. PMID11885988.
Tanida I, Tanida-Miyake E, Nishitani T, Komatsu M, Yamazaki H, Ueno T, Kominami E (Mar 2002). "Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p homologs". Biochemical and Biophysical Research Communications. 292 (1): 256–262. doi:10.1006/bbrc.2002.6645. PMID11890701.
Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (Mar 2002). "Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors". Journal of Neurochemistry. 80 (5): 815–823. doi:10.1046/j.0022-3042.2002.00762.x. PMID11948245.