From owner-diagnostics@net.bio.net Sun Sep 21 23:00:00 1997 Path: biosci!biosci!not-for-mail From: Michal Opas Newsgroups: bionet.diagnostics Subject: Calreticulin Workshop 1998 Date: 22 Sep 1997 01:24:07 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 329 Sender: daemon@net.bio.net Approved: odonnell@sasa.gov.uk Distribution: world Message-ID: <6059v7$ord@net.bio.net> NNTP-Posting-Host: net.bio.net Dear Colleague, We are delighted to announce that Calreticulin Workshop, devoted to the structure and function of calreticulin and related proteins, will take place on March 31 - April 2, 1998 in Banff, Alberta, Canada. The Workshop will provide unique opportunity to meet and interact with the scientists interested in calreticulin research in spectacular surroundings of Banff National Park in Canadian Rocky Mountains. We are sure that the Banff Calreticulin Workshop will be an important forum to share the latest findings and to develop future interactions. Calreticulin has been implicated to play a role in almost every aspect of cell biology as outlined in a brief overview below. We hope that the Workshop will be useful to sort out some of the latest discoveries and controversies concerning calreticulin and implication of this protein in a variety of biological systems. On the behalf of the Organizing Committee we would like to invite you to participate in the Workshop. The Calreticulin Workshop is a satellite meeting to the 8th Fisher Winternational Symposium on Cellular and Molecular Biology which will be held April 2-5, 1998, also at the Banff Conference Centre. The Winternational Symposium, which is co-sponsored by our Society and Fisher Scientific, is held annually, with a different focus each year. The theme for the 1998 meeting is: "Membrane Proteins in Health and Disease." Further information about the meetings and registration forms can be obtained by contacting: Dr. Carol E. Cass, Chair Winternational Symposium Department of Oncology University of Alberta Cross Cancer Institute Edmonton, Alberta T6G 1Z2 phone: (403)432-8320 fax: (403)432-8425 email: sherron.becker@cancerboard.ab.ca website: http://www.csbmcb.ca I hope you participate in Calreticulin Workshop. If you would like to receive further information please send a request as soon as possible (preferably by e-mail) to Michal Opas at: m.opas@utoronto.ca or at: Department of Anatomy & Cell Biology University of Toronto Medical Sciences Building Toronto, Ontario, M5S 1A8 Canada tel: (416) 978-8947 fax: (416) 978-3954 Please note that this is a "last call" for information requests. I look forward to hearing from you in the near future. For The Organizing Committee Sincerely yours Michal Opas Calreticulin, a multifunctional Ca-binding protein Calreticulin, 60 kDa Ca-binding protein [1], is a major component of the endoplasmic reticulum (ER) of non-muscle cells [2-7]. The protein is of high physiological importance as it knockout is embryonic lethal [8]. Along with a wide tissue distribution [9], calreticulin is present in diverse animal and plant species [10]. calreticulin is a resident ER protein as demonstrated by a variety of biochemical and immunological techniques [1,3,4,6,11]. The protein is synthesized with an N-terminal signal sequence and it terminates with the KDEL sequence [3,12] which is responsible for retrieval of proteins to the lumen of the ER [13,14]. Calreticulin functions in vivo as a Ca storage protein [15,16]. It also has been well established that calreticulin is a chaperone [17-21] and it shows similarity in amino acid sequence to a part of calnexin, an ER membrane chaperone [22]. The Ca storage and chaperone functions of calreticulin are consistent with both the ER localization of calreticulin and its structure. Stable overexpression of calreticulin increases both cell-substratum and cell-cell adhesiveness with concomitant upregulation of adhesion-specific cytoskeletal protein, vinculin [23]. Upregulation of calreticulin also affects adhesion-dependent phenomena such as cell motility (which decreases) and cell spreading (which increases). Downregulation of calreticulin brings about inverse effects. In addition to the Ca storage and chaperone function, calreticulin modulates gene expression [24,25]. In vitro, calreticulin interaction with the DNA binding domain of the glucocorticoid receptor prevents the receptor from interacting with its glucocorticoid response element [24]. Transcriptional activation by glucocorticoid and androgen receptors in vivo is inhibited in cells overexpressing full length calreticulin [24,25]. Calreticulin itself is stress-regulated by heat and heavy metals [26-28]. Calreticulin has antithrombotic activity [29]. A host of other putative calreticulin functions includes a role in autoimmune diseases [30-34]. The protein affects replication of the Rubella virus RNA [35,36]. In cytolytic T lymphocytes it is found in the lytic granules where it may play a role in killing of target cells [37]. In human neutrophils calreticulin may contribute to the process of phagocytosis [38]. In line with the reported functional diversity, calreticulin was reported to be present in most cellular compartments [10,11,37,39,40], including the outer cell surface [41,42]. Recent hypotheses regarding calreticulin function have been presented by Krause and Michalak [43]. References 1. Ostwald TJ, MacLennan DH: Isolation of a high affinity calcium binding protein from sarcoplasmic reticulum. J Biol Chem 1974, 249:974-979. 2. Baksh S, Michalak M: Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. J Biol Chem 1991, 266:21458-21465. 3. Fliegel L, Burns K, Opas M, Michalak M: The high-affinity calcium binding protein of sarcoplasmic reticulum. Tissue distribution, and homology with calregulin. Biochim Biophys Acta 1989, 982:1-8. 4. Opas M, Dziak E, Fliegel L, Michalak M: Regulation of expression and intracellular distribution of calreticulin, a major calcium binding protein of nonmuscle cells. J Cell Physiol 1991, 149:160-171. 5. Milner RE, Baksh S, Shemanko C, Carpenter MR, Smillie L, Vance JE, Opas M, Michalak M: Calreticulin, and not calsequestrin, is the major calcium binding protein of smooth muscle sarcoplasmic reticulum and liver endoplasmic reticulum. J Biol Chem 1991, 266:7155-7165. 6. Michalak M, Baksh S, Opas M: Identification and immunolocalization of calreticulin in pancreatic cells: no evidence for "calciosomes". Exp Cell Res 1991, 197:91-99. 7. Michalak M, Milner RE, Burns K, Opas M: Calreticulin. Biochem J 1992, 285:681-692. 8. Coppolino MG, Woodside MJ, Demaurex N, Grinstein S, St-Arnaud R, Dedhar S: Calreticulin is essential for integrin-mediated calcium signalling and cell adhesion. Nature 1997, 386:843-847. 9. Tharin S, Dziak E, Michalak M, Opas M: Widespread tissue distribution of rabbit calreticulin, a non-muscle functional analogue of calsequestrin. Cell Tissue Res 1992, 269:29-37. 10. Opas M: The intracellular distribution and expression of calreticulin. In Calreticulin, edited by Michalak M. Georgetown: R.G. Landes; 1996:31-41. 11. Koch GLE: The endoplasmic reticulum and calcium storage. BioEssays 1990, 12:527-531. 12. Fliegel L, Burns K, MacLennan DH, Reithmeier RAF, Michalak M: Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 1989, 264:21522-21528. 13. Pelham HRB: Control of protein exit from the endoplasmic reticulum. Annu Rev Cell Biol 1989, 5:1-23. 14. S=F6nnichsen B, F=FCllekrug J, Van PN, Diekmann W, Robinson DG, Mieskes G: Retention and retrieval: Both mechanisms cooperate to maintain calreticulin in the endoplasmic reticulum. J Cell Sci 1994, 107:2705-2717. 15. Bastianutto C, Clementi E, Codazzi F, Podini P, De Giorgi F, Rizzuto R, Meldolesi J, Pozzan T: Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol 1995, 130:847-855. 16. Liu N, Fine RE, Simons E, Johnson RJ: Decreasing calreticulin expression lowers the Ca2+ response to bradykinin and increases sensitivity to ionomycin in NG-108-15 cells. J Biol Chem 1994, 269:28635-28639. 17. Nauseef WM, McCormick SJ, Clark RA: Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase. J Biol Chem 1995, 270:4741-4747. 18. Wada I, Imai S, Kai M, Sakane F, Kanoh H: Chaperone function of calreticulin when expressed in the endoplasmic reticulum as the membrane-anchored and soluble forms. J Biol Chem 1995, 270:20298-20304. 19. Nigam SK, Goldberg AL, Ho S, Rhode MF, Bush KT, Sherman MY: A set of endoplasmic reticulum proteins possessing properties of molecular chaperones includes Ca2+-binding proteins and members of the thioredoxin superfamily. J Biol Chem 1994, 269:1744-1749. 20. Otteken A, Moss B: Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. J Biol Chem 1996, 271:97-103. 21. Hebert DN, Foellmer B, Helenius A: Calnexin and calreticulin promote folding, delay oligomerization and suppress degradation of influenza hemagglutinin in microsomes. EMBO J 1996, 15:2961-2968. 22. Bergeron JJM, Brenner MB, Thomas DY, Williams DB: Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem Sci 1994, 19:124-128. 23. Opas M, Szewczenko-Pawlikowski M, Jass GK, Mesaeli N, Michalak M: Calreticulin modulates cell adhesiveness via regulation of vinculin expression. J Cell Biol 1996, 135:1913-1923. 24. Burns K, Duggan B, Atkinson EA, Famulski KS, Nemer M, Bleackley RC, Michalak M: Modulation of gene expression by calreticulin binding to the glucocorticoid receptor. Nature 1994, 367:476-480. 25. Dedhar S, Rennie PS, Shago M, Leung-Hagesteijn C-Y, Yang H, Filmus J, Hawley RG, Bruchovsky N, Cheng H, Matusik RJ, Gigu=E8re V: Inhibition of nuclear hormone receptor activity by calreticulin. Nature 1994, 367:480-483. 26. Nguyen TQ, Capra JD, Sontheimer RD: Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals. Mol Immunol 1996, 33:379-386. 27. Dreher D, Vargas JR, Hochstrasser DF, Junod AF: Effects of oxidative stress and Ca2+ agonists on molecular chaperones in human umbilical vein endothelial cells. Electrophoresis 1995, 16:1205-1214. 28. Conway EM, Liu L, Nowakowski B, Steiner-Mosonyi M, Ribeiro SP, Michalak M: Heat shock-sensitive expression of calreticulin. In vitro and in vivo up-regulation. J Biol Chem 1995, 270:17011-17016. 29. Kuwabara K, Pinsky DJ, Schmidt AM, Benedict C, Brett J, Ogawa S, Broekman MJ, Marcus AJ, Sciacca RR, Michalak M, Wang F, Pan YC, Grunfeld S, Patton S, Malinski T, Stern DM, Ryan J: Calreticulin, an antithrombotic agent which binds to vitamin K-dependent coagulation factors, stimulates endothelial nitric oxide production, and limits thrombosis in canine coronary arteries. J Biol Chem 1995, 270:8179-8187. 30. Karska K, Tuckova L, Steiner L, Tlaskalova-Hogenova H, Michalak M: Calreticulin--the potential autoantigen in celiac disease. Biochem Biophys Res Commun 1995, 209:597-605. 31. Boehm J, Orth T, Van Nguyen P, S=F6ling H-D: Systemic lupus erythematosus is associated with increased auto-antibody titers against calreticulin and grp94, but calreticulin is not the Ro/SS-A antigen. Eur J Clin Invest 1994, 24:248-257. 32. Zhu J, Newkirk MM: Viral induction of the human autoantigen calreticulin. Clin Invest Med 1994, 17:196-205. 33. Ben-Chetrit E: The molecular basis of the SSA/Ro antigens and the clinical significance of their autoantibodies. Br J Rheumatol 1993, 32:396-402. 34. McCauliffe DP, Sontheimer RD: Molecular characterization of the Ro/SS-A autoantigens. J Invest Dermatol 1993, 100:73S-79S. 35. Atreya CD, Singh NK, Nakhasi HL: The rubella virus RNA binding activity of human calreticulin is localized to the N-terminal domain. J Virol 1995, 69:3848-3851. 36. Singh NK, Atreya CD, Nakhasi HL: Identification of calreticulin as a rubella virus RNA binding protein. Proc Natl Acad Sci USA 1994, 91:12770-12774. 37. Dupuis M, Schaerer E, Krause K-H, Tschopp J: The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes. J Exp Med 1993, 177:1-7. 38. Stendahl O, Krause K-H, Krischer J, Jerstrom P, Theler JM, Clark RA, Carpentier JL, Lew DP: Redistribution of intracellular Ca2+ stores during phagocytosis in human neutrophils. Science 1994, 265:1439-1441. 39. Nakamura M, Moriya M, Baba T, Michikawa Y, Yamanobe T, Arai K, Okinaga S, Kobayashi T: An endoplasmic reticulum protein, calreticulin, is transported into the acrosome of rat sperm. Exp Cell Res 1993, 205:101-110. 40. Dedhar S: Novel functions for calreticulin: Interaction with integrins and modulation of gene expression. Trends Biochem Sci 1994, 19:269-271. 41. White TK, Zhu Q, Tanzer ML: Cell surface calreticulin is a putative mannoside lectin which triggers mouse melanoma cell spreading. J Biol Chem 1995, 270:15926-15929. 42. Gray AJ, Park PW, Broekelmann TJ, Laurent GJ, Reeves JT, Stenmark KR, Mecham RP: The mitogenic effects of the B chain of fibrinogen are mediated through cell surface calreticulin. J Biol Chem 1995, 270:26602-26606. 43. Krause K-H, Michalak M: Calreticulin. Cell 1997, 88:439-443. Dr. Michal Opas Department of Anatomy & Cell Biology University of Toronto 1 King's College Circle Medical Sciences Building Toronto, Ontario, M5S 1A8 Canada phone: (416) 978-8947 fax: (416) 978-3954 e-mail: m.opas@utoronto.ca www homepage: http://www.utoronto.ca/anatomy/opas/start.htm .