Calreticulin Meeting: 1st circular

daemon at net.bio.net daemon at net.bio.net
Fri Jul 18 12:21:20 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
=46isher 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
http://www.csbmcb.ca/english/bulletin/winternational.e.html
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.

=46or 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
[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

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Escherichia coli and identification of its Ca2+ binding
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 3. Fliegel L, Burns K, Opas M, Michalak M: The
high-affinity calcium binding protein of sarcoplasmic
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Michalak M: Molecular cloning of the high affinity
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DG, Mieskes G: Retention and retrieval:  Both mechanisms
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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,
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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.

 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.

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function of calreticulin when expressed in the endoplasmic
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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=CBre 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=96ling 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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