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CELSR2

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Target id: 179

Nomenclature: CELSR2

Systematic Nomenclature: ADGRC2

Family: Adhesion Class GPCRs

Contents:

Gene and Protein Information Click here for help
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 2923 1p13.3 CELSR2 cadherin EGF LAG seven-pass G-type receptor 2 8
Mouse 7 2919 3 47.02 cM Celsr2 cadherin, EGF LAG seven-pass G-type receptor 2 17
Rat 7 2144 2q34 Celsr2 cadherin, EGF LAG seven-pass G-type receptor 2
Previous and Unofficial Names Click here for help
MEGF3 | ADGRC2 (adhesion G protein-coupled receptor C2) | multiple epidermal growth factor-like domains 3
Database Links Click here for help
Specialist databases
GPCRdb celr2_human (Hs), celr2_mouse (Mm), celr2_rat (Rn)
Other databases
Alphafold Q9HCU4 (Hs), Q9R0M0 (Mm), Q9QYP2 (Rn)
Ensembl Gene ENSG00000143126 (Hs), ENSMUSG00000068740 (Mm), ENSRNOG00000020058 (Rn)
Entrez Gene 1952 (Hs), 53883 (Mm), 83465 (Rn)
Human Protein Atlas ENSG00000143126 (Hs)
KEGG Gene hsa:1952 (Hs), mmu:53883 (Mm), rno:83465 (Rn)
OMIM 604265 (Hs)
Pharos Q9HCU4 (Hs)
RefSeq Nucleotide NM_001408 (Hs), NM_017392 (Mm), NM_001191110 (Rn)
RefSeq Protein NP_001399 (Hs), NP_059088 (Mm), NP_001178039 (Rn)
UniProtKB Q9HCU4 (Hs), Q9R0M0 (Mm), Q9QYP2 (Rn)
Wikipedia CELSR2 (Hs)
Associated Protein Comments
Extracellular and transmembrane interactors: ADGRC2 [11].
Agonist Comments
No ligands identified: orphan receptor.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Other - See Comments
Comments:  Principal transduction is potentially through Gαq/11 by calcium imaging [11].
Correlation with CamKII activity [11], correlation with Jun Kinase activity [4], increases in intracellular calcium levels associated with Celsr2 and Frizzled-8-positive haemopoetic stem cells under stress (5FU incubation) [14].
References: 
Tissue Distribution Click here for help
Brain
Species:  Human
Technique:  EST
References:  3
Embryo, brain, spinal cord, eye, lung, kidney, spleen, not liver.
Species:  Mouse
Technique:  RT-PCR.
References:  5
Celsr2 is expressed during gastrulation and within the developing nervous system in mouse embryos. Expression patterns are distinct from those of Celsr1 and Celsr3.
Species:  Mouse
Technique:  in situ hybridisation.
References:  6
Pancreas.
Species:  Mouse
Technique:  in situ hybridisation.
References:  4
Haemopoietic stem cells.
Species:  Mouse
Technique:  Microarray analysis.
References:  1,14
Central nervous system.
Species:  Mouse
Technique:  in situ hybridisation.
References:  6,10,12-13,15
Testis.
Species:  Rat
Technique:  in situ hybridisation, immunohistochemistry.
References:  2
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Elevated intracellular calcium levels upon homotypic CELSR2 interactions
Species:  Rat
Tissue:  Hippocampal neurons
Response measured:  Elevated intracellular calcium
References:  11
Physiological Functions Click here for help
Enhanced neurite outgrowth.
Species:  Rat
Tissue:  Hippocampus.
References:  11
Physiological Consequences of Altering Gene Expression Click here for help
Knocking down Celsr2 in rat brain slices resulted in simplification of dendritic arbors of cortical pyramidal neurons and Purkinje neurons. This phenotype seemed to be due to branch retraction.
Species:  Rat
Tissue: 
Technique:  RNAi.
References:  12
Defective tangential neuronal migration. Mice with receptor knockout exhibit defects in the migration of hindbrain neurons.
Species:  Mouse
Tissue:  Full body, brain affected
Technique:  Gene knockout.
References:  9
Mice with receptor knockout exhibit reduced quiescence of haemopoetic stem cells.
Species:  Mouse
Tissue:  Full body, haemopoetic stem cells affected.
Technique:  Gene knockout.
References:  14
Mice with receptor knockout exhibit defects in the development and planar organization of ependymal cilia are compromised, leading to defective CSF dynamics and hydrocephalus.
Species:  Mouse
Tissue:  Fully body, brain affected
Technique:  Gene knockout.
References:  16
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Celsr2tm1Dgen Celsr2tm1Dgen/Celsr2tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1858235  MP:0000825 dilated lateral ventricles
Celsr2+|Celsr2tm1Dgen Celsr2tm1Dgen/Celsr2+
involves: 129P2/OlaHsd * C57BL/6		 MGI:1858235  MP:0000825 dilated lateral ventricles
General Comments
CELSR2 (cadherin, EGF LAG seven-pass G-type receptor 2) is a receptor that belongs to Family IV Adhesion-GPCRs together with CELSR2 and CELSR3 [7]. Family IV Adhesion-GPCRs have orthologs in vertebrate and invertebrate species.

References

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1. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J, Li L. (2003) Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood, 101 (2): 383-9. [PMID:12393558]

2. Beall SA, Boekelheide K, Johnson KJ. (2005) Hybrid GPCR/cadherin (Celsr) proteins in rat testis are expressed with cell type specificity and exhibit differential Sertoli cell-germ cell adhesion activity. J Androl, 26 (4): 529-38. [PMID:15955893]

3. Bjarnadóttir TK, Geirardsdóttir K, Ingemansson M, Mirza MA, Fredriksson R, Schiöth HB. (2007) Identification of novel splice variants of Adhesion G protein-coupled receptors. Gene, 387 (1-2): 38-48. [PMID:17056209]

4. Cortijo C, Gouzi M, Tissir F, Grapin-Botton A. (2012) Planar cell polarity controls pancreatic Beta cell differentiation and glucose homeostasis. Cell Rep, 2 (6): 1593-606. [PMID:23177622]

5. Formstone CJ, Barclay J, Rees M, Little PF. (2000) Chromosomal localization of Celsr2 and Celsr3 in the mouse; Celsr3 is a candidate for the tippy (tip) lethal mutant on chromosome 9. Mamm Genome, 11 (5): 392-4. [PMID:10790539]

6. Formstone CJ, Little PF. (2001) The flamingo-related mouse Celsr family (Celsr1-3) genes exhibit distinct patterns of expression during embryonic development. Mech Dev, 109: 91-94. [PMID:11677057]

7. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun, 301 (3): 725-34. [PMID:12565841]

8. Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N. (1996) Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain. DNA Res, 3 (5): 321-9, 341-54. [PMID:9039502]

9. Qu Y, Glasco DM, Zhou L, Sawant A, Ravni A, Fritzsch B, Damrau C, Murdoch JN, Evans S, Pfaff SL, Formstone C, Goffinet AM, Chandrasekhar A, Tissir F. (2010) Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. J Neurosci, 30 (28): 9392-401. [PMID:20631168]

10. Shima Y, Copeland NG, Gilbert DJ, Jenkins NA, Chisaka O, Takeichi M, Uemura T. (2002) Differential expression of the seven-pass transmembrane cadherin genes Celsr1-3 and distribution of the Celsr2 protein during mouse development. Dev Dyn, 223 (3): 321-32. [PMID:11891983]

11. Shima Y, Kawaguchi SY, Kosaka K, Nakayama M, Hoshino M, Nabeshima Y, Hirano T, Uemura T. (2007) Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nat Neurosci, 10 (8): 963-9. [PMID:17618280]

12. Shima Y, Kengaku M, Hirano T, Takeichi M, Uemura T. (2004) Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin. Dev Cell, 7 (2): 205-16. [PMID:15296717]

13. Stevens CF, Williams JH. (2000) "Kiss and run" exocytosis at hippocampal synapses. Proc Natl Acad Sci USA, 97 (23): 12828-33. [PMID:11050187]

14. Sugimura R, He XC, Venkatraman A, Arai F, Box A, Semerad C, Haug JS, Peng L, Zhong XB, Suda T et al.. (2012) Noncanonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell, 150 (2): 351-65. [PMID:22817897]

15. Tissir F, Goffinet AM. (2006) Expression of planar cell polarity genes during development of the mouse CNS. Eur J Neurosci, 23 (3): 597-607. [PMID:16487141]

16. Tissir F, Qu Y, Montcouquiol M, Zhou L, Komatsu K, Shi D, Fujimori T, Labeau J, Tyteca D, Courtoy P, Poumay Y, Uemura T, Goffinet AM. (2010) Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat Neurosci, 13 (6): 700-7. [PMID:20473291]

17. Usui T, Shima Y, Shimada Y, Hirano S, Burgess RW, Schwarz TL, Takeichi M, Uemura T. (1999) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell, 98 (5): 585-95. [PMID:10490098]

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