Calretinin

Calbindin 2
Identifiers
Symbols	CALB2 ; CAB29; CAL2; CR
External IDs	OMIM: 114051 MGI: 101914 HomoloGene: 1318 GeneCards: CALB2 Gene
Gene ontology Molecular function • calcium ion binding Cellular component • nucleus • cytoplasm • cytosol • gap junction • neuron projection • terminal bouton • synapse Biological process • cytosolic calcium ion homeostasis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	794	12308
Ensembl	ENSG00000172137	ENSMUSG00000003657
UniProt	P22676	Q08331
RefSeq (mRNA)	NM_001740	NM_007586
RefSeq (protein)	NP_001731	NP_031612
Location (UCSC)	Chr 16: 71.36 – 71.39 Mb	Chr 8: 110.14 – 110.17 Mb
PubMed search

Micrograph of a malignant epithelioid mesothelioma stained with an antibody against calretinin.

Calretinin also known as 29 kDa calbindin is a calcium-binding protein involved in calcium signaling.^[1] In humans, the calretinin protein is encoded by the CALB2 gene.^[2][3]

Function

This gene encodes an intracellular calcium-binding protein belonging to the troponin C superfamily. Members of this protein family have six EF-hand domains which bind calcium. This protein plays a role in diverse cellular functions, including message targeting and intracellular calcium buffering.^[2]

Calretinin is abundantly expressed in neurons including retina (which gave it the name)^[1] and cortical interneurons.^[4] Expression was found in different neurons than that of the similar vitamin D-dependent calcium-binding protein, calbindin-28kDa.^[1]

Calretinin has an important role as a modulator of neuronal excitability including the induction of long-term potentiation.^[5] Loss of expression of calretinin in hippocampal interneurons has been suggested to be relevant in temporal lobe epilepsy.^[6]

It is expressed in a number of other locations including hair follicles.^[7]

Clinical significance

Calretinin is a diagnostic marker for some human diseases, including Hirschsprung disease and some cancers.

Mesothelioma

Using immunohistochemistry, calretinin can be demonstrated in both benign mesothelium and in malignant mesothelioma^[8][9] and can be used to help differentiate different lung tumours.^[10] Antibodies to calretinin can also be used to distinguish between different types of brain tumour, demonstrating only those with neuronal rather than glial, differentiation.^[11] Furthermore, the essential function of calretinin in mesothelioma cell lines has been demonstrated in vitro and may be an interesting target for therapeutical approaches.^[12]

Hirschsprung disease

In Hirschsprung disease, calretinin immunohistochemistry offers additional diagnostic value in specimens with inadequate amount of submucosa and rarely seen ganglion cells. The presence of ganglion cells consistently correlated with calretinin-positive thin nerve fibrils in the lamina propria, muscularis mucosae and superficial submucosa. These calretinin-positive thin neurofibrils are absent in the aganglionic segments of bowel and in the areas without ganglion cells from the junction of normal with diseased rectum. Calretinin is strongly expressed in the submucosal and subserosal nerve trunks in the ganglionic segment. No calretinin expression is seen in the nerve trunks in the rest of the aganglionic segment. It has faint expression in the thick nerve trunks from the areas without ganglion cells. Faint positivity of the thick submucosal and subserosal nerves in the absence of ganglion cells and calretinin positive nerve fibrils, is characteristic of the junction of the aganglionic-to-normal rectum.^[13]

References

1. Rogers JH (1987). "Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons.". J Cell Biol 105 (3): 1343–53. doi:10.1083/jcb.105.3.1343. PMC 2114790. PMID 3654755.
2. "Entrez Gene: calbindin 2".
3. Parmentier M, Passage E, Vassart G, Mattei MG (1991). "The human calbindin D28k (CALB1) and calretinin (CALB2) genes are located at 8q21.3----q22.1 and 16q22----q23, respectively, suggesting a common duplication with the carbonic anhydrase isozyme loci". Cytogenetics and Cell Genetics 57 (1): 41–3. doi:10.1159/000133111. PMID 1906795.
4. Barinka F, Druga R (2010). "Calretinin expression in the mammalian neocortex: a review.". Physiol Res 59 (5): 665–77. PMID 20406030.
5. Camp AJ, Wijesinghe R (2009). "Calretinin: modulator of neuronal excitability.". Int J Biochem Cell Biol 41 (11): 2118–21. doi:10.1016/j.biocel.2009.05.007. PMID 19450707.
6. Tóth K, Maglóczky Z (2014). "The vulnerability of calretinin-containing hippocampal interneurons to temporal lobe epilepsy.". Front Neuroanat 8: 100. doi:10.3389/fnana.2014.00100. PMC 4179514. PMID 25324731.
7. Poblet E, Jimenez F, de Cabo C, Prieto-Martin A, Sánchez-Prieto R (Jun 2005). "The calcium-binding protein calretinin is a marker of the companion cell layer of the human hair follicle". The British Journal of Dermatology 152 (6): 1316–20. doi:10.1111/j.1365-2133.2005.06603.x. PMID 15948999.
8. Saydan N, Salicio V, Cappelli-Gotzos B, Gotzos V (2001). "Expression of calretinin in human mesothelioma cell lines and cell cycle analysis by flow cytometry". Anticancer Research 21 (1A): 181–8. PMID 11299732.
9. Gotzos, V.; Vogt, P.; Celio, M. R. (1996-02-01). "The calcium binding protein calretinin is a selective marker for malignant pleural mesotheliomas of the epithelial type". Pathology, Research and Practice 192 (2): 137–147. doi:10.1016/S0344-0338(96)80208-1. ISSN 0344-0338. PMID 8692714.
10. Marchevsky AM (Mar 2008). "Application of immunohistochemistry to the diagnosis of malignant mesothelioma". Archives of Pathology & Laboratory Medicine 132 (3): 397–401. doi:10.1043/1543-2165(2008)132[397:AOITTD]2.0.CO;2. PMID 18318582.
11. Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 45–46. ISBN 1-84110-100-1.
12. Blum, Walter; Schwaller, Beat (2013-11-01). "Calretinin is essential for mesothelioma cell growth/survival in vitro: a potential new target for malignant mesothelioma therapy?". International Journal of Cancer 133 (9): 2077–2088. doi:10.1002/ijc.28218. ISSN 1097-0215. PMID 23595591.
13. Alexandrescu S, Rosenberg H, Tatevian N (2013). "Role of calretinin immunohistochemical stain in evaluation of Hirschsprung disease: an institutional experience". International Journal of Clinical and Experimental Pathology 6 (12): 2955–61. PMC 3843278. PMID 24294384.

Further reading

• Alaeddini M, Etemad-Moghadam S, Baghaii F (Feb 2008). "Comparative expression of calretinin in selected odontogenic tumours: a possible relationship to histogenesis". Histopathology 52 (3): 299–304. doi:10.1111/j.1365-2559.2007.02948.x. PMID 18269580.
• Guinard-Samuel V, Bonnard A, De Lagausie P, Philippe-Chomette P, Alberti C, El Ghoneimi A, Peuchmaur M, Berrebi-Binczak D (Oct 2009). "Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease". Modern Pathology 22 (10): 1379–84. doi:10.1038/modpathol.2009.110. PMID 19648883.
• Seress L, Abrahám H, Czéh B, Fuchs E, Léránth C (2008). "Calretinin expression in hilar mossy cells of the hippocampal dentate gyrus of nonhuman primates and humans". Hippocampus 18 (4): 425–34. doi:10.1002/hipo.20403. PMID 18189312.
• Zhang H, Bu H, Chen H, Wei B, Liu W, Guo J, Li F, Liao D, Tang Y, Zhang Z (Jan 2008). "Comparison of immunohistochemical markers in the differential diagnosis of adrenocortical tumors: immunohistochemical analysis of adrenocortical tumors". Applied Immunohistochemistry & Molecular Morphology 16 (1): 32–9. doi:10.1097/PAI.0b013e318032cf56. PMID 18091323.
• Vonlanthen S, Kawecki TJ, Betticher DC, Pfefferli M, Schwaller B (2007). "Heterozygosity of SNP513 in intron 9 of the human calretinin gene (CALB2) is a risk factor for colon cancer". Anticancer Research 27 (6C): 4279–88. PMID 18214032.
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (Mar 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
• Lee ES, Leong AS, Kim YS, Lee JH, Kim I, Ahn GH, Kim HS, Chun YK (Mar 2006). "Calretinin, CD34, and alpha-smooth muscle actin in the identification of peritoneal invasive implants of serous borderline tumors of the ovary". Modern Pathology 19 (3): 364–72. doi:10.1038/modpathol.3800539. PMID 16415795.
• Iio K, Nagasawa Y, Iwatani H, Yamamoto R, Horii A, Okuzaki D, Furumatsu Y, Inohara H, Nojima H, Imai E, Isaka Y, Rakugi H (Mar 2010). "Microarray analysis of tonsils in immunoglobulin A nephropathy patients". Biochemical and Biophysical Research Communications 393 (4): 565–70. doi:10.1016/j.bbrc.2010.01.120. PMID 20138841.
• DeVilliers P, Liu H, Suggs C, Simmons D, Daly B, Zhang S, Raubenheimer E, Larsson A, Wright T (Feb 2008). "Calretinin expression in the differential diagnosis of human ameloblastoma and keratocystic odontogenic tumor". The American Journal of Surgical Pathology 32 (2): 256–60. doi:10.1097/PAS.0b013e3181452176. PMID 18223328.
• Portugal R, Oliva E (Mar 2009). "Calretinin: diagnostic utility in the female genital tract". Advances in Anatomic Pathology 16 (2): 118–24. doi:10.1097/PAP.0b013e31819923ce. PMID 19550372.
• Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB (Mar 2009). "Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation". Human Pathology 40 (3): 398–404. doi:10.1016/j.humpath.2008.08.014. PMC 2657293. PMID 18992917.
• Melotti A, Daga A, Marubbi D, Zunino A, Mutti L, Corte G (2010). "In vitro and in vivo characterization of highly purified human mesothelioma derived cells". BMC Cancer 10: 54. doi:10.1186/1471-2407-10-54. PMC 2850899. PMID 20175889.
• Häner K, Henzi T, Pfefferli M, Künzli E, Salicio V, Schwaller B (Feb 2010). "A bipartite butyrate-responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells". Journal of Cellular Biochemistry 109 (3): 519–31. doi:10.1002/jcb.22429. PMID 19998412.
• Henzi T, Blum WV, Pfefferli M, Kawecki TJ, Salicio V, Schwaller B (Jun 2009). "SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis". The American Journal of Pathology 174 (6): 2324–36. doi:10.2353/ajpath.2009.080352. PMC 2684196. PMID 19435792.
• Barinka F, Druga R, Marusic P, Krsek P, Zamecnik J (Jan 2010). "Calretinin immunoreactivity in focal cortical dysplasias and in non-malformed epileptic cortex". Epilepsy Research 88 (1): 76–86. doi:10.1016/j.eplepsyres.2009.09.021. PMID 19854615.
• Mai KT, Teo I, Al Moghrabi H, Marginean EC, Veinot JP (Aug 2008). "Calretinin and CD34 immunoreactivity of the endometrial stroma in normal endometrium and change of the immunoreactivity in dysfunctional uterine bleeding with evidence of 'disordered endometrial stroma'". Pathology 40 (5): 493–9. doi:10.1080/00313020802197897. PMID 18604736.
• Massouh M, Wallman MJ, Pourcher E, Parent A (Dec 2008). "The fate of the large striatal interneurons expressing calretinin in Huntington's disease". Neuroscience Research 62 (4): 216–24. doi:10.1016/j.neures.2008.08.007. PMID 18801393.
• Rougemont AL, Sartelet H, Oligny LL, Bensoussan A, Yazbeck S, Fournet JC (2007). "Accessory liver lobe with mesothelial inclusion cysts in an omphalocele: a new malformative association". Pediatric and Developmental Pathology 10 (3): 224–8. doi:10.2350/06-08-0148.1. PMID 17535091.
• Clements RJ, McDonough J, Freeman EJ (May 2008). "Distribution of parvalbumin and calretinin immunoreactive interneurons in motor cortex from multiple sclerosis post-mortem tissue". Experimental Brain Research 187 (3): 459–65. doi:10.1007/s00221-008-1317-9. PMID 18297277.

External links

• calretinin at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.