Calreticulin workshop

Michal Opas m.opas at utoronto.ca
Mon Sep 22 07:10:48 EST 1997

 Dear Colleagues,

 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 at 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 at 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 
 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 
 	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].
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 calcium binding protein from sarcoplasmic reticulum. J Biol 
 Chem 1974, 249:974-979.
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  3. Fliegel L, Burns K, Opas M, Michalak M: The 
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 smooth muscle sarcoplasmic reticulum and liver endoplasmic 
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  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.
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 Biochem J 1992, 285:681-692.
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 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 
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 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. Sönnichsen B, Füllekrug 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, 
  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, 
  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, Giguère 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, 
  30. Karska K, Tuckova L, Steiner L, Tlaskalova-Hogenova H, 
 Michalak M: Calreticulin--the potential autoantigen in 
 celiac disease. Biochem Biophys Res Commun 1995, 
  31. Boehm J, Orth T, Van Nguyen P, Söling 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, 
      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 at utoronto.ca
       www homepage: http://www.utoronto.ca/anatomy/opas/start.htm 

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