鈣黏素
![](http://upload.wikimedia.org/wikipedia/commons/thumb/2/27/Adherens_Junctions_structural_proteins.svg/350px-Adherens_Junctions_structural_proteins.svg.png)
鈣黏素[1](cadherins,calcium-dependent adhesion))又稱鈣黏着蛋白[2][註 1]、鈣黏合素,是一類I型跨膜糖蛋白,由日本科學家竹市雅俊發現並命名。它們在細胞連接中扮演重要角色,保證了細胞在組織中彼此結合。發揮它們的功能需要鈣離子(Ca2+),因此得名。
鈣黏素超家族包括:鈣黏蛋白,原鈣黏蛋白(protocadherin),橋粒黏蛋白(desmogleins),橋粒膠蛋白(desmocollins)等。[3][4]它們在結構方面,共享了「鈣黏素重複」的胞外鈣離子-結合結構域。鈣黏素分為若干類型,每一類用一個前綴表示(一般地,表示了其與哪一類組織相關)。已在細胞培養和發育過程中觀察到,包含某一特定鈣黏素亞型的細胞趨向於簇集在一起而排斥包含其他類別的細胞。[來源請求]例如,包含N-鈣黏素的細胞趨向於同其他表達N-鈣黏素的細胞聚集在一起。然而,也要注意到細胞培養實驗中,混合速度可以影響其同型(homotypic)特異性的程度。[5]此外,其他若干小組在不同的實驗中觀察到異型結合親和性(即,不同類型的鈣黏素結合在一起)。[6][7]目前一種模型主張細胞基於動力學特異性而非熱力學特異性來區分鈣黏素亞型,理由是不同的鈣黏素同型鍵具有不同的壽命。[8]
類型
[編輯]鈣黏素家族的不同成員在不同的位置出現。E-鈣黏素位於上皮組織;N-鈣黏素在神經元中;P-鈣黏素在胎盤中。T-鈣黏素沒有胞漿結構域且必須系鏈到質膜上。[來源請求]
(上皮)E-鈣黏素是研究最為透徹的鈣黏素家族成員。它由胞外結構域5個鈣黏素重複(EC1~EC5),一個跨膜結構域及一個結合p120連環素-和ß-連環素的胞內結構域組成。胞內結構域包括一個高度磷酸化的區域,該區域對其與ß-連環素的結合,繼而對於E-鈣黏素的功能至關重要。[來源請求] 上皮細胞中,含E-鈣黏素的細胞間連接經常毗鄰含肌動蛋白的細胞骨架的微絲。
E-鈣黏素首先表達在哺乳動物發育的2細胞期,在8細胞期被磷酸化,而導致緊密化(compaction)。[來源請求]成年組織中,E-鈣黏素在上皮組織中表達,以5小時的半衰期在細胞表面持續更新。[來源請求]
癌症的發展和轉移牽涉了E-鈣黏素功能或表達的缺失。[來源請求] E-鈣黏素下調降低了一個組織內細胞黏附的強度,導致細胞活動性(motility)增加。[來源請求]這可以轉而允許癌細胞穿過基底膜入侵周圍組織。
E-鈣黏素也被病理學家用於診斷不同類型的乳腺癌。與浸潤性導管癌相比,免疫組化研究中大部分浸潤性小葉癌的E-鈣黏素表達明顯減少或消失。[9]
備註
[編輯]- ^ 由於「黏蛋白」(mucin)與「黏着蛋白」、「黏附蛋白」(adhesin)意義不同,術語在線未採用「鈣-黏蛋白」此翻譯。
參見
[編輯]參考資料
[編輯]- ^ 存档副本. [2021-07-14]. (原始內容存檔於2021-07-14).
- ^ 存档副本. [2021-07-14]. (原始內容存檔於2021-07-14).
- ^ Hulpiau P, van Roy F. Molecular evolution of the cadherin superfamily. Int. J. Biochem. Cell Biol. February 2009, 41 (2): 349–69. PMID 18848899. doi:10.1016/j.biocel.2008.09.027.
- ^ Angst B, Marcozzi C, Magee A. The cadherin superfamily: diversity in form and function. J Cell Sci. February 2001, 114 (Pt 4): 629–41. PMID 11171368.
- ^ Duguay, D.; A. Foty R., RA; S. Steinberg M., MS. Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev. Biol. 2003, 253 (2): 309–323. PMID 12645933. doi:10.1016/S0012-1606(02)00016-7.
- ^ Niessen, Carien M.; Gumbiner, Barry M. Cadherin-mediated cell sorting not determined by binding or adhesion specificity. The Journal of Cell Biology. 2002, 156 (2): 389. PMC 2199232
. PMID 11790800. doi:10.1083/jcb.200108040.
- ^ Volk, T.; Cohen, O.; Geiger, B. Formation of heterotypic adherens-type junctions between L-CAM containing liver cells and A-CAM containing lens cells. Cell. 1987, 50 (6): 987–994. PMID 3621349. doi:10.1016/0092-8674(87)90525-3.
- ^ Bayas, Marco V.; Leung, Andrew; Evans, Evan; Leckband, Deborah. Lifetime Measurements Reveal Kinetic Differences between Homophilic Cadherin Bonds. Biophysical Journal. 2005, 90 (4): 1385. PMC 1367289
. PMID 16326909. doi:10.1529/biophysj.105.069583.
- ^ Rosen, P. Rosen's Breast Pathology, 3rd ed, 2009, p. 704. Lippincott Williams & Wilkins.
延伸閱讀
[編輯]- Beavon IR. The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation. Eur. J. Cancer. 2000, 36 (13 Spec No): 1607–20. PMID 10959047. doi:10.1016/S0959-8049(00)00158-1.
- Berx G, Becker KF, Höfler H, van Roy F. Mutations of the human E-cadherin (CDH1) gene. Hum. Mutat. 1998, 12 (4): 226–37. PMID 9744472. doi:10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D.
- Bryant DM, Stow JL. The ins and outs of E-cadherin trafficking. Trends Cell Biol. 2005, 14 (8): 427–34. PMID 15308209. doi:10.1016/j.tcb.2004.07.007.
- Chun YS, Lindor NM, Smyrk TC, et al. Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?. Cancer. 2001, 92 (1): 181–7. PMID 11443625. doi:10.1002/1097-0142(20010701)92:1<181::AID-CNCR1307>3.0.CO;2-J.
- Georgolios A, Batistatou A, Manolopoulos L, Charalabopoulos K. Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC). J. Exp. Clin. Cancer Res. 2006, 25 (1): 5–14. PMID 16761612.
- Hazan RB, Qiao R, Keren R, et al. Cadherin switch in tumor progression. Ann. N. Y. Acad. Sci. 2004, 1014 (1): 155–63. PMID 15153430. doi:10.1196/annals.1294.016.
- Moran CJ, Joyce M, McAnena OJ. CDH1 associated gastric cancer: a report of a family and review of the literature. Eur J Surg Oncol. 2005, 31 (3): 259–64. PMID 15780560. doi:10.1016/j.ejso.2004.12.010.
- Reynolds AB, Carnahan RH. Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer. Semin. Cell Dev. Biol. 2005, 15 (6): 657–63. PMID 15561585. doi:10.1016/j.semcdb.2004.09.003.
- Wang HD, Ren J, Zhang L. CDH1 germline mutation in hereditary gastric carcinoma. World J. Gastroenterol. 2004, 10 (21): 3088–93. PMID 15457549.
- Wijnhoven BP, Dinjens WN, Pignatelli M. E-cadherin-catenin cell-cell adhesion complex and human cancer. The British journal of surgery. 2000, 87 (8): 992–1005. PMID 10931041. doi:10.1046/j.1365-2168.2000.01513.x.
- Wilson PD. Polycystin: new aspects of structure, function, and regulation. J. Am. Soc. Nephrol. 2001, 12 (4): 834–45. PMID 11274246.
- Renaud-Young M, Gallin WJ. In the first extracellular domain of E-cadherin, heterophilic interactions, but not the conserved His-Ala-Val motif, are required for adhesion. Journal of Biological Chemistry. 2002, 277 (42): 39609–39616. PMID 12154084. doi:10.1074/jbc.M201256200.
外部連結
[編輯]- Cadherin domain (頁面存檔備份,存於互聯網檔案館) in PROSITE
- The cadherin family
- Alberts, Bruce. Molecular Biology of the Cell (頁面存檔備份,存於互聯網檔案館)
- The Cadherin Resource (頁面存檔備份,存於互聯網檔案館)
- IPR002126
- [1] (頁面存檔備份,存於互聯網檔案館)
- 「Cadherin adhesome at a glance」. J Cell Sci 126, 373-378 (頁面存檔備份,存於互聯網檔案館)
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