Talk:Calreticulin
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request to add history
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Hello, I am David M. Waisman, a biochemist whose research has included work on endoplasmic reticulum calcium‑binding proteins and a recent historical review on calreticulin (“Calreticulin—Enigmatic Discovery”, 2024). Because this represents a conflict of interest under Wikipedia’s policies, I am not editing the article directly, but I would like to request that editors consider adding a short, sourced “History and discovery” subsection to the Calreticulin article. At present, the article does not describe the discovery history of calreticulin. The literature distinguishes between early work on a hepatic endoplasmic reticulum Ca2+-binding protein (calregulin/CRP55) and later sequence‑based consolidation under the name “calreticulin,” as well as a more controversial connection to a previously described skeletal muscle high‑affinity calcium‑binding protein (HACBP). My recent review and earlier primary papers summarize this development and may help provide a neutral, sourced overview. I would be grateful if the editors could review these sources and, if appropriate, adapt or refine the proposed text to align with Wikipedia’s neutrality and sourcing policies. I am happy to clarify any points about the cited literature here on the Talk page.
History and discovery[edit]History and discovery Calreticulin was first identified in the early 1980s as a calcium‑binding protein in liver, where it was purified from the 100,000×g supernatant and characterized as a novel cytosolic calcium‑binding protein distinct from calmodulin [ref 1]. A subsequent study isolated and characterized a related Ca²⁺‑binding protein (CAB‑63, formerly called calregulin) and established its basic biochemical properties [ref 2]. Further work on calregulin demonstrated its purification, cellular localization, and tissue distribution, showing that it is a high‑capacity, low‑affinity Ca²⁺‑binding protein localized to the endoplasmic reticulum (ER) lumen of hepatocytes rather than the cytosol, and that it is conserved across vertebrate livers [ref 3]. These studies established calregulin as an ER luminal Ca²⁺‑binding protein with properties distinct from cytosolic Ca²⁺‑binding proteins such as calmodulin. In 1989, Smith and Koch cloned and sequenced an ER protein previously known as CRP55 and proposed the name calreticulin for this major Ca²⁺‑binding protein of the ER [ref 5]. Their sequence analysis and immunological data indicated that several previously described proteins, including CRP55 and calregulin, correspond to the same gene product. Around the same time, Fliegel and colleagues reported that the high‑affinity calcium‑binding protein (HACBP) of skeletal muscle SR shares N‑terminal sequence homology with calregulin and is widely distributed in non‑muscle tissues, suggesting that HACBP and calregulin are closely related or identical [ref 6]. A subsequent molecular cloning study from the same group cloned the cDNA for the skeletal muscle SR HACBP, and designated the encoded protein as calreticulin, thereby explicitly equating HACBP with calreticulin [ref 7]. A recent historical review has re‑examined these primary data and concluded that the most reproducible biochemical and cell‑biological evidence supports identification of calreticulin as an ER luminal Ca²⁺‑binding protein first characterized in liver (calregulin/CAB‑63), and that the skeletal muscle SR HACBP reports rest on irreproducible findings and are best interpreted as experimental artefacts rather than independent, reproducible discoveries of calreticulin in skeletal muscle [ref 8]. On this basis, that review describes the discovery of calreticulin as a multi‑step process: initial identification and characterization of a hepatic Ca²⁺‑binding protein (calregulin/CAB‑63), subsequent localization to the ER and recognition of high conservation across vertebrate livers, sequence‑based consolidation of related names (CRP55, calregulin and HACBP) under the term calreticulin, and later reinterpretation of the skeletal muscle HACBP literature in light of these findings.
Waisman, D. M., Salimath, B. P., Anderson, M. J. (1985). "Isolation and characterization of CAB-63, a novel calcium- binding protein". Journal of Biological Chemistry. 260 (3): 1652–1660.. Khanna, N. C., Tokuda, M., Waisman, D. M. (1987). "Calregulin: purification, cellular localization, and tissue distribution". Methods Enzymol. 139: 36–50.. Khanna, N. C., Tokuda, M., Waisman, D. M. (15 February 1987). "Comparison of calregulins from vertebrate livers". Biochemical Journal. 242 (1): 245–251. ISSN 0264-6021.. Smith, M. J., Koch, G. L. (1 December 1989). "Multiple zones in the sequence of calreticulin (CRP55, calregulin, HACBP), a major calcium binding ER/SR protein". The EMBO journal. 8 (12): 3581–3586. ISSN 0261-4189.. Fliegel, L., Burns, K., Opas, M., Michalak, M. (26 June 1989). "The high-affinity calcium binding protein of sarcoplasmic reticulum. Tissue distribution, and homology with calregulin". Biochimica Et Biophysica Acta. 982 (1): 1–8. ISSN 0006-3002.. Fliegel, L., Burns, K., MacLennan, D. H., Reithmeier, R. A., Michalak, M. (25 December 1989). "Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum". The Journal of Biological Chemistry. 264 (36): 21522–21528. ISSN 0021-9258.. Okura, G. C., Bharadwaj, A. G., Waisman, D. M. (19 July 2024). "Calreticulin-Enigmatic Discovery". Biomolecules. 14 (7): 866. doi:10.3390/biom14070866. ISSN 2218-273X. |
Dmwaisman (talk) 15:25, 19 April 2026 (UTC)
Reply 20-JUN-2026
[edit]- Specific page numbers for these articles were not appended to the request. Needless to say, the COI editor ought not expect the COI reviewer to read 53 pages of text in order to verify these claims.
Regards, Spintendo 20:00, 20 June 2026 (UTC)


