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 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]
↑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. PMID1906795.
↑Barinka F, Druga R (2010). "Calretinin expression in the mammalian neocortex: a review". Physiol Res. 59 (5): 665–77. PMID20406030.
↑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. PMID15948999.
↑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. PMID11299732.
↑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. ISBN1-84110-100-1.
↑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. ISSN1097-0215. PMID23595591.
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. PMID18269580.
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. PMID19648883.
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. PMID18189312.
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. PMID18091323.
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. PMID18214032.
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. PMID18029348.
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. PMID16415795.
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. PMID20138841.
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. PMID18223328.
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. PMID19550372.
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. PMID19998412.
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. PMID19854615.
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. PMID18604736.
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. PMID18801393.
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