G protein-coupled receptor 126 juga dikenal sebagai VIGR dan DREG adalah protein yang disandir oleh gen ADGRG6.[5][6][7] GPR126 adalah anggota dari famili GPCR adhesi.[8][9] GPCR adhesi ditandai oleh daerah ekstraseluler diperpanjang sering memiliki modul protein N-terminal yang terhubung ke wilayah TM7 melalui domain dikenal sebagai domain GPCR-Autoproteolysis INducing (GAIN).[10]

ADGRG6
Identifiers
AliasesADGRG6, APG1, DREG, PS1TP2, VIGR, GPR126, LCCS9, adhesion G protein-coupled receptor G6, PR126
External IDsOMIM: 612243 MGI: 1916151 HomoloGene: 10724 GeneCards: ADGRG6
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for ADGRG6
Genomic location for ADGRG6
Band6q24.2Start142,301,854 bp[1]
End142,446,266 bp[1]
RNA expression pattern
PBB GE GPR126 213094 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001032394
NM_001032395
NM_020455
NM_198569

NM_001002268

RefSeq (protein)

NP_001027566
NP_001027567
NP_065188
NP_940971

NP_001002268

Location (UCSC)Chr 6: 142.3 – 142.45 MbChr 10: 14.4 – 14.55 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

GPR126 secara luas diekspresikan pada sel-sel stroma.[11] Fragmen N-terminal dari GPR126 mengandung C1r-C1s, Uegf dan Bmp1 (CUB), dan PTX-like modules.[12]

LiganSunting

GPR126 ditunjukkan untuk mengikat kolagen IV dan laminin-211 mempromosikan siklik adenosin monofosfat (cAMP) untuk memperantarai mielinisasi.[13][14]

PensinyalanSunting

Setelah stimulasi lipopolisakarida (LPS) atau thrombin, ekspresi GPR126 diinduksi oleh MAP Kinase pada sel endotelial.[12] Selama angiogenesis, GPR126 mendorong pensinyalan teraktivasi protein kinase A (PKA)–cAMP pada sel endotelial.[15] Ekspresi ektopik GPR126 pada sel COS-7 meningkatkan level cAMP dengan koupling heterotrimerik protein Gαs/i.[16]

FungsiSunting

GPR126 berperan penting dalam mielinasi sel SchwannSunting

Dalam sistem saraf vertebrata, banyak akson dikelilingi oleh selubung mielin untuk melakukan potensial aksi cepat dan efisien. Dengan menggunakan skrining genetik dalam mutan ikan zebra, kelompok penelitian Talbot menunjukkan bahwa GPR126 mempengaruhi perkembangan akson termielinisasi.[17] GPR126 mendorong diferensiasi sel Schwann melalui induksi level cAMP, yang menyebabkan aktivitas transkripsional Oct6 untuk mempromosikan aktivitas gen mielin.[18] Mutasi gpr126 pada ikan zebra mempengaruhi mielinisasi perifer. Kelompok penelitian Monk menunjukkan fungsi domain-spesifik GPR126 selama perkembangan sel Schwann: NTF perlu dan cukup untuk menyortir akson, sedangkan CTF mempromosikan membungkus melalui induksi level cAMP untuk mengatur tahap awal dan akhir perkembangan sel Schwann.[14]

ReferensiSunting

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000112414 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039116 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. 
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB (Feb 2003). "There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini". Biochemical and Biophysical Research Communications. 301 (3): 725–34. doi:10.1016/S0006-291X(03)00026-3. PMID 12565841. 
  6. ^ "Entrez Gene: GPR126 G protein-coupled receptor 126". 
  7. ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMID 25713288. 
  8. ^ Stacey M, Yona S (2011). Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN 1-4419-7912-3. 
  9. ^ Langenhan T, Aust G, Hamann J (21 May 2013). "Sticky signaling--adhesion class G protein-coupled receptors take the stage". Science signaling. 6 (276): re3. doi:10.1126/scisignal.2003825. PMID 23695165. 
  10. ^ Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT (Mar 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–78. doi:10.1038/emboj.2012.26. PMC 3321182 . PMID 22333914. 
  11. ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB (Apr 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMID 25713288. 
  12. ^ a b Stehlik C, Kroismayr R, Dorfleutner A, Binder BR, Lipp J (Jul 2004). "VIGR--a novel inducible adhesion family G-protein coupled receptor in endothelial cells". FEBS Letters. 569 (1-3): 149–55. doi:10.1016/j.febslet.2004.05.038. PMID 15225624. 
  13. ^ Paavola KJ, Sidik H, Zuchero JB, Eckart M, Talbot WS (Aug 2014). "Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126". Science Signaling. 7 (338): ra76. doi:10.1126/scisignal.2005347. PMID 25118328. 
  14. ^ a b Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR (Feb 2015). "The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211". Neuron. 85 (4): 755–69. doi:10.1016/j.neuron.2014.12.057. PMID 25695270. 
  15. ^ Cui H, Wang Y, Huang H, Yu W, Bai M, Zhang L, Bryan BA, Wang Y, Luo J, Li D, Ma Y, Liu M (Dec 2014). "GPR126 protein regulates developmental and pathological angiogenesis through modulation of VEGFR2 receptor signaling". The Journal of Biological Chemistry. 289 (50): 34871–85. doi:10.1074/jbc.M114.571000. PMID 25217645. 
  16. ^ Mogha A, Benesh AE, Patra C, Engel FB, Schöneberg T, Liebscher I, Monk KR (Nov 2013). "Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation". The Journal of Neuroscience. 33 (46): 17976–85. doi:10.1523/JNEUROSCI.1809-13.2013. PMID 24227709. 
  17. ^ Pogoda HM, Sternheim N, Lyons DA, Diamond B, Hawkins TA, Woods IG, Bhatt DH, Franzini-Armstrong C, Dominguez C, Arana N, Jacobs J, Nix R, Fetcho JR, Talbot WS (Oct 2006). "A genetic screen identifies genes essential for development of myelinated axons in zebrafish". Developmental Biology. 298 (1): 118–31. doi:10.1016/j.ydbio.2006.06.021. PMID 16875686. 
  18. ^ Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C, Moens CB, Talbot WS (Sep 2009). "A G protein-coupled receptor is essential for Schwann cells to initiate myelination". Science. 325 (5946): 1402–5. doi:10.1126/science.1173474. PMID 19745155.