GABARAP explained
Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.[1]
Function
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.
Interactions
GABARAP has been shown to interact with TFRC,[4] ULK1[5] [6] and GABRG2.[7] [8] A bound structure for GABARAP to GABRG2 consistent with experimental observations has been computationally derived.[9]
References
Further reading
- Kanematsu T, Hirata M . [The analysis of protein-protein interaction with special reference to PRIP-1] . Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica . 119 . 4 . 241–6 . Apr 2002 . 11979730 . 10.1254/fpj.119.241 . free .
- Paz Y, Elazar Z, Fass D . Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p . The Journal of Biological Chemistry . 275 . 33 . 25445–25450 . Aug 2000 . 10856287 . 10.1074/jbc.C000307200 . free .
- Wang H, Olsen RW . 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 . Aug 2000 . 10899939 . 10.1046/j.1471-4159.2000.0750644.x . 86634862 . free .
- Kneussel M, Haverkamp S, Fuhrmann JC, Wang H, Wässle H, Olsen RW, Betz H . The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse . Proceedings of the National Academy of Sciences of the United States of America . 97 . 15 . 8594–8599 . Jul 2000 . 10900017 . 26993 . 10.1073/pnas.97.15.8594 . 2000PNAS...97.8594K . free .
- Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL . Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning . Proceedings of the National Academy of Sciences of the United States of America . 97 . 17 . 9543–9548 . Aug 2000 . 10931946 . 16901 . 10.1073/pnas.160270997 . 2000PNAS...97.9543H . free .
- Chen L, Wang H, Vicini S, Olsen RW . The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics . Proceedings of the National Academy of Sciences of the United States of America . 97 . 21 . 11557–11562 . Oct 2000 . 10984509 . 17239 . 10.1073/pnas.190133497 . 2000PNAS...9711557C . free .
- Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–1560 . Oct 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
- Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M . 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 . Dec 2000 . 11146101 . 10.1016/S0169-328X(00)00218-7 .
- Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S . Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein . Genomics . 74 . 3 . 408–413 . Jun 2001 . 11414770 . 10.1006/geno.2001.6555 .
- Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ . 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 . Jul 2001 . 11461150 . 10.1006/mcne.2001.1005 . 43244403 .
- Stangler T, Mayr LM, Dingley AJ, Luge C, Willbold D . Sequence-specific 1H, 13C and 15N resonance assignments of human GABA receptor associated protein . Journal of Biomolecular NMR . 21 . 2 . 183–4 . Oct 2001 . 11727985 . 10.1023/A:1012416810974 . 31757286 .
- Harris R, McAlister MS, Sankar A, Phelan JP, Moss SJ, Keep NH, Driscoll PC . 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 . Oct 2001 . 11727986 . 10.1023/A:1012473609468 . 82224217 .
- Knight D, Harris R, McAlister MS, Phelan JP, Geddes S, Moss SJ, Driscoll PC, Keep NH . 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 . Feb 2002 . 11729197 . 10.1074/jbc.M109753200 . free .
- Coyle JE, Qamar S, Rajashankar KR, Nikolov DB . Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding . Neuron . 33 . 1 . 63–74 . Jan 2002 . 11779480 . 10.1016/S0896-6273(01)00558-X . 14487823 . free .
- Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E . 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 . Apr 2002 . 11825910 . 10.1074/jbc.M200385200 . free .
- Stangler T, Mayr LM, Willbold D . 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 . Apr 2002 . 11875056 . 10.1074/jbc.C200050200 . free .
- Kouno T, Miura K, Kanematsu T, Shirakawa M, Hirata M, Kawano K . 1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor associated protein . Journal of Biomolecular NMR . 22 . 1 . 97–98 . Jan 2002 . 11885988 . 10.1023/A:1013884402033 . 82980835 .
- Tanida I, Tanida-Miyake E, Nishitani T, Komatsu M, Yamazaki H, Ueno T, Kominami E . Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p homologs . Biochemical and Biophysical Research Communications . 292 . 1 . 256–262 . Mar 2002 . 11890701 . 10.1006/bbrc.2002.6645 .
- Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW . Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors . Journal of Neurochemistry . 80 . 5 . 815–823 . Mar 2002 . 11948245 . 10.1046/j.0022-3042.2002.00762.x . 38049055 .
Notes and References
- Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW . GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton . Nature . 397 . 6714 . 69–72 . Jan 1999 . 9892355 . 10.1038/16264 . 204990449 .
- Web site: Entrez Gene: GABARAP GABA(A) receptor-associated protein.
- Szalai P, Hagen LK, Sætre F, Luhr M, Sponheim M, Øverbye A, Mills IG, Seglen PO, Engedal N . Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs . Experimental Cell Research . 333 . 1 . 21–38 . 2015 . 25684710 . 10.1016/j.yexcr.2015.02.003 .
- Green F, O'Hare T, Blackwell A, Enns CA . Association of human transferrin receptor with GABARAP . FEBS Letters . 518 . 1–3 . 101–106 . May 2002 . 11997026 . 10.1016/S0014-5793(02)02655-8 . 29391940 . free .
- 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 . 17353931 . 1847948 . 10.1038/msb4100134 . 2007 .
- Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M . 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 . Dec 2000 . 11146101 . 10.1016/S0169-328X(00)00218-7 .
- Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW . Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors . Journal of Neurochemistry . 80 . 5 . 815–823 . Mar 2002 . 11948245 . 10.1046/j.0022-3042.2002.00762.x . 38049055 .
- Coyle JE, Qamar S, Rajashankar KR, Nikolov DB . Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding . Neuron . 33 . 1 . 63–74 . Jan 2002 . 11779480 . 10.1016/S0896-6273(01)00558-X . 14487823 . free .
- Irwin BW, Vukovic S, Payne MC, ElGamacy M, Chau PL . Prediction of GABARAP interaction with the GABA type A receptor . Proteins . 86 . 12 . 1251–1264 . Dec 2018 . 30218455 . 6492159 . 10.1002/prot.25589 .