GPR56

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GPR56 adalah anggota dari GPCR adhesi (adhesion GPCR).^[1]

Ligan

Ligan-ligan yang berinteraksi dengan GPR56:

Ekspresi

GPR56 diekspresikan pada:

sel NK CD56^dim manusia
sel T CD27^-CD45RA⁺ (sel T sitotoksik reaktif)
sel NK memori-like berumur panjang^[5]

Ekspresi GPR56 diinduksi oleh faktor transkripsi Hobit (homolog of Blimp-1). Pada manusia, Hobit diekspresikan pada sel NK dan sel T quiescent, sangat dekat kecocokannya dengan ekspresi GPR56.^[6]

Peran GPR56

GPR56 banyak berperan dalam proses-proses berikut:

pembentukan dan penjagaan sel puncak hematopoietik
perkembangan kortikal
kesuburan pria
hipertropi otot
pertumbuhan dan progesi melanoma
reseptor penghambat pada sel NK^[5]
menghambat migrasi sel NK baik secara spontan maupun distimulasi SDF-1^[7]

Mutasi pada GPR56

Mutasi pada GPR56 menyebabkan malformasi otak manusia dinamakan bilateral frontoparietal polymicrogyria (BFPP).^[8] Ada 13 mutasi berbeda pada pasien BFPP, termasuk 1 delesi, 2 splicing, dan 10 mutasi missense.^[8] Jenis-jenis mutasi:

R565W, terjadi mutasi pada simpul ekstraseluler kedua

mutasi ini menghambat ekspresi reseptor di permukaan sel

R38Q
R38W
Y88C
C91S

keempat mutasi terjadi pada ujung N, menghasilkan protein dengan penurunan lalu lintas intraselular dan rendahnya ekspresi pada permukaan sel

C346S
W349S

kedua mutasi ini terjadi pada domain GAIN membuat protein dengan pemecahan terganggu secara dramatis sehingga gagal diangkut ke retikulum endoplasma

Transduksi sinyal

Molekul sinyal yang terlibat dalam transduksi sinyal GPR56 meliputi:

Gαq/11^[9]
Gα12/13 dan aktivasi RhoA^[10]^[11]^[12]
PKCα
mTOR

Referensi

^ Langenhan T, Aust G, Hamann J (2007). "Sticky signaling--adhesion class G protein-coupled receptors take the stage". Sci Signal. 6 (276). doi:10.1126/scisignal.2003825. PMID 23695165.
^ Xu L, Begum S, Hearn JD, Hynes RO (2006). "GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis". Proc Natl Acad Sci USA. 103 (24): 9023–8. PMC 1474142 . PMID 16757564.
^ Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X (2011). "G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination". Proc Natl Acad Sci USA. 108 (31): 12925–30. doi:10.1073/pnas.1104821108. PMC 3150909 . PMID 21768377.
^ Chiang NY, Chang GW, Huang YS, Peng YM, Hsiao CC, Kuo ML, Lin HH (2016). "Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility". J Cell Sci. 129 (11). doi:10.1242/jcs.174458. PMID 27068534.
^ ^a ^b Chang GW, Hsiao CC, Peng YM, Vieira Braga FA, Kragten NA, Remmerswaal EB, et al. (2016). "The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells". Cell Rep. 15 (8): 1757–70. doi:10.1016/j.celrep.2016.04.053. PMID 27184850.
^ Vieira Braga FA, Hertoghs KM, Kragten NA, Doody GM, Barnes NA, Remmerswaal EB, et al. (2015). "Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans". Eur J Immunol. 45 (10): 2945–58. doi:10.1002/eji.201545650. PMID 26179882.
^ Peng YM, van de Garde MD, Cheng KF, Baars PA, Remmerswaal EB, van Lier RA, et al. (2011). "Specific expression of GPR56 by human cytotoxic lymphocytes". J Leukoc Biol. 90 (4): 735–40. doi:10.1189/jlb.0211092. PMID 21724806.
^ ^a ^b Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, et al. (2004). "G protein-coupled receptor-dependent development of human frontal cortex". Science. 303 (5666): 2033–6. PMID 15044805.
^ Little KD, Hemler ME, Stipp CS (2004). "Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association". Mol Biol Cell. 15 (5): 2375–87. PMC 404030 . PMID 15004227.
^ Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H (2008). "Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway". J Biol Chem. 283 (21): 14469–78. doi:10.1074/jbc.M708919200. PMID 18378689.
^ Ackerman SD, Garcia C, Piao X, Gutmann DH, Monk KR (2016). "The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA". Nat Commun. 6 (6122). doi:10.1038/ncomms7122. PMC 4302765 . PMID 25607772.
^ Giera S, Deng Y, Luo R, Ackerman SD, Mogha A, Monk KR, et al. (2015). "The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development". Nat Commun. 6 (6121). doi:10.1038/ncomms7121. PMC 4302951 . PMID 25607655.

[1] Langenhan T, Aust G, Hamann J (2007). "Sticky signaling--adhesion class G protein-coupled receptors take the stage". Sci Signal. 6 (276). doi:10.1126/scisignal.2003825. PMID 23695165.

[2] Xu L, Begum S, Hearn JD, Hynes RO (2006). "GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis". Proc Natl Acad Sci USA. 103 (24): 9023–8. PMC 1474142 . PMID 16757564.

[3] Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X (2011). "G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination". Proc Natl Acad Sci USA. 108 (31): 12925–30. doi:10.1073/pnas.1104821108. PMC 3150909 . PMID 21768377.

[4] Chiang NY, Chang GW, Huang YS, Peng YM, Hsiao CC, Kuo ML, Lin HH (2016). "Heparin interacts with the adhesion GPCR GPR56, reduces receptor shedding, and promotes cell adhesion and motility". J Cell Sci. 129 (11). doi:10.1242/jcs.174458. PMID 27068534.

[nk-5] Chang GW, Hsiao CC, Peng YM, Vieira Braga FA, Kragten NA, Remmerswaal EB, et al. (2016). "The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells". Cell Rep. 15 (8): 1757–70. doi:10.1016/j.celrep.2016.04.053. PMID 27184850.

[6] Vieira Braga FA, Hertoghs KM, Kragten NA, Doody GM, Barnes NA, Remmerswaal EB, et al. (2015). "Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans". Eur J Immunol. 45 (10): 2945–58. doi:10.1002/eji.201545650. PMID 26179882.

[7] Peng YM, van de Garde MD, Cheng KF, Baars PA, Remmerswaal EB, van Lier RA, et al. (2011). "Specific expression of GPR56 by human cytotoxic lymphocytes". J Leukoc Biol. 90 (4): 735–40. doi:10.1189/jlb.0211092. PMID 21724806.

[piao-8] Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R, et al. (2004). "G protein-coupled receptor-dependent development of human frontal cortex". Science. 303 (5666): 2033–6. PMID 15044805.

[9] Little KD, Hemler ME, Stipp CS (2004). "Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association". Mol Biol Cell. 15 (5): 2375–87. PMC 404030 . PMID 15004227.

[10] Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H (2008). "Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway". J Biol Chem. 283 (21): 14469–78. doi:10.1074/jbc.M708919200. PMID 18378689.

[11] Ackerman SD, Garcia C, Piao X, Gutmann DH, Monk KR (2016). "The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA". Nat Commun. 6 (6122). doi:10.1038/ncomms7122. PMC 4302765 . PMID 25607772.

[12] Giera S, Deng Y, Luo R, Ackerman SD, Mogha A, Monk KR, et al. (2015). "The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development". Nat Commun. 6 (6121). doi:10.1038/ncomms7121. PMC 4302951 . PMID 25607655.

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