Roles of Calreticulin in Protein Folding, Immunity, Calcium Signaling and Cell Transformation

Prog Mol Subcell Biol. 2021:59:145-162. doi: 10.1007/978-3-030-67696-4_7.

Abstract

The endoplasmic reticulum (ER) is an organelle that mediates the proper folding and assembly of proteins destined for the cell surface, the extracellular space and subcellular compartments such as the lysosomes. The ER contains a wide range of molecular chaperones to handle the folding requirements of a diverse set of proteins that traffic through this compartment. The lectin-like chaperones calreticulin and calnexin are an important class of structurally-related chaperones relevant for the folding and assembly of many N-linked glycoproteins. Despite the conserved mechanism of action of these two chaperones in nascent protein recognition and folding, calreticulin has unique functions in cellular calcium signaling and in the immune response. The ER-related functions of calreticulin in the assembly of major histocompatibility complex (MHC) class I molecules are well-studied and provide many insights into the modes of substrate and co-chaperone recognition by calreticulin. Calreticulin is also detectable on the cell surface under some conditions, where it induces the phagocytosis of apoptotic cells. Furthermore, mutations of calreticulin induce cell transformation in myeloproliferative neoplasms (MPN). Studies of the functions of the mutant calreticulin in cell transformation and immunity have provided many insights into the normal biology of calreticulin, which are discussed.

Keywords: Calcium signaling; Calnexin; Calreticulin; Major Histocompatibility Complex (MHC) class I; Myeloproliferative neoplasms; PDIA3; Phagocytosis of apoptotic cells.

MeSH terms

  • Calcium Signaling* / genetics
  • Calnexin / genetics
  • Calnexin / metabolism
  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Immune System
  • Protein Folding

Substances

  • Calreticulin
  • Calnexin