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Calreticulin Meeting: 1st circular

Michal Opas m.opas at utoronto.ca
Fri Jul 18 11:44:59 EST 1997

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 Fisher 
Winternational or the satellite meetings can be obtained by 
visiting the Society's web site at 
or by contacting the Chair of the Scientific Program 
Committee by E-mail:  Carol Cass <carol.cass at ualberta.ca.>.

I hope you will participate in the Calreticulin Workshop.  
If you would like to receive further information please send 
a request (if possible, 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

I look forward to hearing from you in the near future.

For The Organizing Committee
Sincerely yours
Michal Opas

       Calreticulin, a multifunctional 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].


 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, 

 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, 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, 

 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, 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, 
     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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