GABARAP
A proteína associada ao receptor de ácido gama-aminobutírico (do inglês: Gamma-aminobutyric acid receptor-associated protein) é uma proteína que em humanos é codificada pelo gene GABARAP.
Função
Os receptores do ácido gama-aminobutírico A [receptores GABA (A)] são canais de cloreto dependentes de ligantes que mediam a neurotransmissão inibitória. Esse gene codifica a proteína associada ao receptor GABA (A), que é altamente carregada positivamente em seu terminal N e compartilha a similaridade de sequência com a cadeia leve-3 das proteínas 1A e 1B associadas ao microtúbulo. Essa proteína agrupa receptores de neurotransmissores por mediar a interação com o citoesqueleto.
Além disso, o GABARAP tem uma função importante na autofagia mediada por autofagossomo, uma vez que é crucial para a formação de autofagossomo e sequestro de carga citosólica em vesículas de membrana dupla, levando à subsequente degradação após a fusão com lisossomos. Além disso, o GABARAP pode mediar a autofagia seletiva porque se liga aos chamados receptores autofágicos (por exemplo, p62, NBr1), que vinculam e recrutam cargas específicas.
Interações
Foi demonstrado que o GABARAP interage com o TFRC, ULK1 e GABRG2. Uma estrutura ligada entre GABARAP e GABRG2 consistente com observações experimentais foi derivada computacionalmente.
Referências
- 1 2 Moss SJ, Olsen RW, Wang H, Bedford FK, Brandon NJ. «GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton». Nature. 397: 69–72. PMID 9892355. doi:10.1038/16264
- ↑ «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 (2015). «Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs». Experimental Cell Research. 333: 21–38. PMID 25684710. doi:10.1016/j.yexcr.2015.02.003
- ↑ Green F, O'Hare T, Blackwell A, Enns CA. «Association of human transferrin receptor with GABARAP» (PDF). FEBS Letters. 518: 101–106. PMID 11997026. doi:10.1016/S0014-5793(02)02655-8
- ↑ 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 (2007). «Large-scale mapping of human protein-protein interactions by mass spectrometry». Molecular Systems Biology. 3. 89 páginas. PMC 1847948
. PMID 17353931. doi:10.1038/msb4100134 - ↑ 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: 1–12. PMID 11146101. doi: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: 815–823. PMID 11948245. doi:10.1046/j.0022-3042.2002.00762.x
- ↑ 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: 63–74. PMID 11779480. doi:10.1016/S0896-6273(01)00558-X
- ↑ Irwin BW, Vukovic S, Payne MC, ElGamacy M, Chau PL. «Prediction of GABARAP interaction with the GABA type A receptor». Proteins. 86: 1251–1264. doi:10.1002/prot.25589
Leitura adicional
- Kanematsu T, Hirata M (abril de 2002). «[The analysis of protein-protein interaction with special reference to PRIP-1]». Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 119 (4): 241–6. PMID 11979730. doi:10.1254/fpj.119.241
- Paz Y, Elazar Z, Fass D (agosto de 2000). «Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p». The Journal of Biological Chemistry. 275 (33): 25445–25450. PMID 10856287. doi:10.1074/jbc.C000307200
- Wang H, Olsen RW (agosto de 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. PMID 10899939. doi:10.1046/j.1471-4159.2000.0750644.x
- Kneussel M, Haverkamp S, Fuhrmann JC, Wang H, Wässle H, Olsen RW, Betz H (julho de 2000). «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. PMC 26993. PMID 10900017. doi:10.1073/pnas.97.15.8594
- 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 (agosto de 2000). «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. PMC 16901. PMID 10931946. doi:10.1073/pnas.160270997
- Chen L, Wang H, Vicini S, Olsen RW (outubro de 2000). «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. PMC 17239. PMID 10984509. doi:10.1073/pnas.190133497
- 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 (outubro de 2000). «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. PMC 310934. PMID 11042152. doi:10.1101/gr.140200
- Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M (dezembro de 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. PMID 11146101. doi: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 (junho de 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. PMID 11414770. doi:10.1006/geno.2001.6555
- Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ (julho de 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. PMID 11461150. doi:10.1006/mcne.2001.1005
- Stangler T, Mayr LM, Dingley AJ, Luge C, Willbold D (outubro de 2001). «Sequence-specific 1H, 13C and 15N resonance assignments of human GABA receptor associated protein». Journal of Biomolecular NMR. 21 (2): 183–4. PMID 11727985. doi:10.1023/A:1012416810974
- Harris R, McAlister MS, Sankar A, Phelan JP, Moss SJ, Keep NH, Driscoll PC (outubro de 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. PMID 11727986. doi:10.1023/A:1012473609468
- Knight D, Harris R, McAlister MS, Phelan JP, Geddes S, Moss SJ, Driscoll PC, Keep NH (fevereiro de 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. PMID 11729197. doi:10.1074/jbc.M109753200
- Coyle JE, Qamar S, Rajashankar KR, Nikolov DB (janeiro de 2002). «Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding». Neuron. 33 (1): 63–74. PMID 11779480. doi:10.1016/S0896-6273(01)00558-X
- Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E (abril de 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. PMID 11825910. doi:10.1074/jbc.M200385200
- Stangler T, Mayr LM, Willbold D (abril de 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. PMID 11875056. doi:10.1074/jbc.C200050200
- Kouno T, Miura K, Kanematsu T, Shirakawa M, Hirata M, Kawano K (janeiro de 2002). «1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor associated protein». Journal of Biomolecular NMR. 22 (1): 97–98. PMID 11885988. doi:10.1023/A:1013884402033
- Tanida I, Tanida-Miyake E, Nishitani T, Komatsu M, Yamazaki H, Ueno T, Kominami E (março de 2002). «Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p homologs». Biochemical and Biophysical Research Communications. 292 (1): 256–262. PMID 11890701. doi:10.1006/bbrc.2002.6645
- Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (março de 2002). «Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors». Journal of Neurochemistry. 80 (5): 815–823. PMID 11948245. doi:10.1046/j.0022-3042.2002.00762.x
