Calreticulin Workshop 1998

Michal Opas m.opas at utoronto.ca
Mon Sep 22 03:24:07 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 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 
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].

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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.

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functions as a molecular chaperone in the biosynthesis of 
myeloperoxidase. J Biol Chem 1995, 270:4741-4747.

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MY: A set of endoplasmic reticulum proteins possessing 
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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.

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Michalak M: Calreticulin modulates cell adhesiveness via 
regulation of vinculin expression. J Cell Biol 1996, 
135:1913-1923.

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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 
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270:8179-8187.

 30. Karska K, Tuckova L, Steiner L, Tlaskalova-Hogenova H, 
Michalak M: Calreticulin--the potential autoantigen in 
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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.

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antigens and the clinical significance of their 
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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 at utoronto.ca
www homepage: http://www.utoronto.ca/anatomy/opas/start.htm 
   





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