| Structural highlights
Function
[AGRG1_MOUSE] Receptor involved in cell adhesion and probably in cell-cell interactions. Mediates cell matrix adhesion in developing neurons and hematopoietic stem cells. Receptor for collagen III/COL3A1 in the developing brain and involved in regulation of cortical development, specifically in maintenance of the pial basement membrane integrity and in cortical lamination (PubMed:21768377). Binding to the COL3A1 ligand inhibits neuronal migration and activates the RhoA pathway by coupling to GNA13 and possibly GNA12 (By similarity). Plays a role in the maintenance of hematopoietic stem cells and/or leukemia stem cells in bone marrow niche (PubMed:23478665). Plays a critical role in tumourigenesis (By similarity). Plays essential role in testis development (PubMed:20981830).[UniProtKB:Q9Y653][1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology.
Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains.,Salzman GS, Ackerman SD, Ding C, Koide A, Leon K, Luo R, Stoveken HM, Fernandez CG, Tall GG, Piao X, Monk KR, Koide S, Arac D Neuron. 2016 Sep 21;91(6):1292-1304. doi: 10.1016/j.neuron.2016.08.022. PMID:27657451[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H. Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem. 2008 May 23;283(21):14469-78. doi: 10.1074/jbc.M708919200. Epub 2008, Mar 31. PMID:18378689 doi:http://dx.doi.org/10.1074/jbc.M708919200
- ↑ Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008 May 28;28(22):5817-26. doi: 10.1523/JNEUROSCI.0853-08.2008. PMID:18509043 doi:http://dx.doi.org/10.1523/JNEUROSCI.0853-08.2008
- ↑ Koirala S, Jin Z, Piao X, Corfas G. GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci. 2009 Jun 10;29(23):7439-49. doi: 10.1523/JNEUROSCI.1182-09.2009. PMID:19515912 doi:http://dx.doi.org/10.1523/JNEUROSCI.1182-09.2009
- ↑ Chen G, Yang L, Begum S, Xu L. GPR56 is essential for testis development and male fertility in mice. Dev Dyn. 2010 Dec;239(12):3358-67. doi: 10.1002/dvdy.22468. PMID:20981830 doi:http://dx.doi.org/10.1002/dvdy.22468
- ↑ Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X. G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12925-30. doi:, 10.1073/pnas.1104821108. Epub 2011 Jul 18. PMID:21768377 doi:http://dx.doi.org/10.1073/pnas.1104821108
- ↑ Saito Y, Kaneda K, Suekane A, Ichihara E, Nakahata S, Yamakawa N, Nagai K, Mizuno N, Kogawa K, Miura I, Itoh H, Morishita K. Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56. Leukemia. 2013 Aug;27(8):1637-49. doi: 10.1038/leu.2013.75. Epub 2013 Mar 12. PMID:23478665 doi:http://dx.doi.org/10.1038/leu.2013.75
- ↑ Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E, Wang PP, Murayama AY, Im K, Lisgo SN, Overman L, Sestan N, Chang BS, Barkovich AJ, Grant PE, Topcu M, Politsky J, Okano H, Piao X, Walsh CA. Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science. 2014 Feb 14;343(6172):764-8. doi: 10.1126/science.1244392. PMID:24531968 doi:http://dx.doi.org/10.1126/science.1244392
- ↑ Salzman GS, Ackerman SD, Ding C, Koide A, Leon K, Luo R, Stoveken HM, Fernandez CG, Tall GG, Piao X, Monk KR, Koide S, Arac D. Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains. Neuron. 2016 Sep 21;91(6):1292-1304. doi: 10.1016/j.neuron.2016.08.022. PMID:27657451 doi:http://dx.doi.org/10.1016/j.neuron.2016.08.022
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