Chapter category: Cell Metabolism

Introduction to Calreticulin

This chapter appears in the following book:

Calreticulin
Second Edition

Edited by: Paul Eggleton and Marek Michalak
ISBN: 0-306-47845-5
» Get more information about this book at landesbioscience.com «

Chapter authors:
Paul Eggleton and Marek Michalak

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Over 30 years ago calreticulin, then known as the high affinity calcium binding protein (HACBP), was identified and purified from isolated skeletal muscle sarcoplasmic reticulum vesicles.1,2 Surprisingly, it took almost 20 years to realize that the protein is a major component of the endoplasmic reticulum (ER) in non-muscle cells3. However, today, calreticulin is considered one of the best markers for the ER. In 1989 isolation of cDNA encoding calreticulin was reported3,4 and provided a useful tool to carry out biochemical, molecular biological and cell biological studies of the protein. This led to a number of advances on the structure and function of calreticulin. The recent application of calreticulin gene deletion in mice,5,6 C. elegans7,8 and in Dictyostelium9 have led to exciting discoveries of the role of calreticulin in organogenesis and several pathologies. Moreover, long awaited structural studies on calreticulin10 and calnexin11 provided the first insights into 3D structure of ER luminal proteins and their domains. This will have a tremendous impact on the future studies on these and other ER chaperones. The first edition of calreticulin book was published in 1996 and encompassed a series of diverse articles introducing this peculiar protein to the World.12 In the last 6 years, chaperone and Ca2+ binding functions of calreticulin have been well described and are now wildly accepted. New and exciting areas of research have emerged focusing now on the role of calreticulin and other ER protein in diseases including protein folding disorders, cardiac pathologies, cancer and autoimmunity. The protein has attracted a lot of attention in many diverse areas of basic and now clinical research. The popularity in this protein has led to the organization of a number of international workshops specifically on the function of calreticulin. The first International Workshop on calreticulin was held in Banff, Alberta, Canada in 1994. This was followed by 4 further workshops now alternating between European and North American locations on a biannual basis: in 1996 in Como, Italy;13 in 1998 in Banff, Alberta,14 in 2000 in Oxford, UK15 and in 2002 in San Antonio, Texas, USA. In addition, an exciting research session organized by Michal Opas (University of Toronto) dedicated to calreticulin was included at the meeting of the American Cell Biology Society in San Francisco in 1996.16

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Additional chapters from this book:

Calreticulin Deficient Mouse

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Calreticulin, from its initial discovery, has been considered a multifunctional protein.1 Indeed, many diverse functions have been attributed to this protein, including roles in protein folding ...

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Byung-Jae Park, Jin Il Lee and Joohong Ahnn

The nematode C. elegans is an ideal organism to study the in vivo genetic and biochemical functions of calreticulin. In vitro studies show that the C. elegans CRT-1 protein, like other calreticu...

The Hookworm Calreticulin Conundrum

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Hookworm parasites possess effective defence mechanisms against host innate and adaptive immune responses such as complement activation, eosinophilia and the respiratory burst in granulocytes. H...

Role of Calreticulin in Leishmania Parasite Secretory Pathway and Pathogenesis

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Cell Surface Calreticulin: Role in Signaling Thrombospondin Anti-Adhesive Activity

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Cell adhesion is a multi-step process initiated by receptor binding to extracellular matrix (ECM) components. This triggers intracellular signaling cascades leading to spreading and organization...

Calreticulin’s Role(s) in Autoimmune Disorders

Richard D. Sontheimer, Doina Racila, Emil Racila, Paul Eggleton

For over ten years autoantibodies (Aab) against calreticulin (CRT) have been reported in a number of autoimmune disorders including rheumatoid arthritis, Sjögren’s syndrome, celiac disease an...

Calreticulin and Tumor Suppression

Giovanna Tosato, Lei Yao and Sandra E. Pike

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Calreticulin in Cytotoxic Lymphocyte-Mediated Cytotoxicity

Dorothy Hudig and Reza Karimi

New functions are implicated for calreticulin, based on its release from cytotoxic NK and T cells. Calreticulin is the only one of six "KDEL" (Lys-Asp-Glu-Leu carboxy terminal) endoplasmic retic...

ER Calcium and ER Chaperones: New Players in Apoptosis?

Nicolas Demaurex, Maud Frieden and Serge Arnaudeau

By using calcium ions as an intracellular messenger, cells walk a tight rope between life and death. Because critical cellular functions depend on the precise delivery of Ca2+ at the right time ...

Calnexin and Calreticulin, ER Associated Modulators of Calcium Transport in the ER

Patricia Camacho, Linu John, Yun Li, R. Madelaine Paredes

Calreticulin (CRT) and calnexin (CNX) are members of a family of endoplasmic reticulum (ER) chaperones that fold newly synthesized polypeptides. Aside from their role as foldases in the ER, our ...

Modulation of Calcium Homeostasis by the Endoplasmic Reticulum in Health and Disease

György Szabadkai, Mounia Chami, Paolo Pinton and Rosario Rizzuto

The endoplasmic reticulum (ER) is the main intracellular agonist-sensitive Ca2+ store, and is involved in the regulation of a wide range of cellular functions depending on cytosolic Ca2+. In addit...

Calreticulin and the Endoplasmic Reticulum in Plant Cell Biology

Paola Mariani, Lorella Navazio and Anna Zuppini

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Raju Adhikari and Tim Elliott

Assembly of Major Histocompatibility Complex (MHC) class I heavy chain (HC) with b2-microglobulin (b2m) and subsequent acquisition of optimal peptides is necessary for class I antigen presentati...

Calreticulin-Mediated Nuclear Protein Export

Ben E. Black and Bryce M. Paschal

The role of calreticulin (CRT) as a molecular chaperone that functions in the endoplasmic reticulum (ER) is well established. This involves transient binding of CRT to hydrophobic residues and c...

Roles of Calreticulin and Calnexin in Myeloperoxidase Synthesis

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Calnexin and Calreticulin, Molecular Chaperones of the Endoplasmic Reticulum

Michael R. Leach and David B. Williams

In this chapter we present the evidence that calnexin (CNX) and calreticulin (CRT) function as molecular chaperones to assist in the folding and subunit assembly of the majority of Asn-linked glycopr...

Sub-Cellular Distribution of Calreticulin

Sylvia Papp and Michal Opas

Calreticulin is a KDEL-containing protein, yet in many cell types and under variable conditions, it has been found outside of its major residence, the endoplasmic reticulum. While the mechanism(...

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John J.M. Bergeron and David Y. Thomas

This review discusses the ER protein calnexin that is related in structure and function to calreticulin. In vivo and in vitro experiments from many laboratories have provided evidence that calnexin an...

A Chaperone System for Glycoprotein Folding: The Calnexin/Calreticulin Cycle

Lars Ellgaard and Ari Helenius

The endoplasmic reticulum (ER) contains a particularly wide range of molecular chaperones and other proteins that assist the folding and quality control of newly synthesized protein. Some, like ...

Biochemical and Molecular Properties of Calreticulin

Steven J. Johnson and Kjell O. Håkansson

Calreticulin is a highly abundant Ca2+-storage protein found in all cells of higher organisms, with the exception of erythrocytes. It is predominantly located in the endoplasmic reticulum where,...

Introduction to Calreticulin

Paul Eggleton and Marek Michalak

Over 30 years ago calreticulin, then known as the high affinity calcium binding protein (HACBP), was identified and purified from isolated skeletal muscle sarcoplasmic reticulum vesicles.1,2 Sur...

Chapter category: Cell Metabolism

Introduction to Calreticulin

Additional chapters from this book:

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