<abstract xmlns="http://www.w3.org/1999/xhtml">

Calreticulin (CALR) is a highly conserved multi-function protein that primarily localizes within the lumen of the endoplasmic reticulum (ER). It participates in various processes in the cells, including glycoprotein chaperoning, regulation of Ca2+ homeostasis, antigen processing and presentation for adaptive immune response, cell adhesion/migration, cell proliferation, immunogenic cell death, gene expression and RNA stability. The role of CALR in the assembly, retrieval and cell surface expression of MHC class I molecules is well known. A fraction of the total cellular CALR is localized in the cytosol, following its retro-translocation from the ER. In the cell stress conditions, CALR is also expressed on the cell surface via an interaction with phosphatidylserine localized on the inner leaflet of the plasma membrane. The abovementioned mechanism is relevant for the recognition of the cells, as well as immunogenicity and phagocytic uptake of proapoptotic and apoptotic cells.
Lastly, the presence of <italic>CALR</italic> exon 9 gene mutations was confirmed in patients with myeloproliferative neoplasms. Their presence results in an abnormal CALR structure due to the loss of its ER-retention sequence, CALR extra-ER localisation, the formation of a complex with thrombopoietin receptor, and oncogenic transformation of hematopoietic stem cells. It is also known that <italic>CALR</italic> exon 9 mutants are highly immunogenic and induce T cell response. Despite this fact, <italic>CALR</italic> mutant positive hematopoietic cells emerge. The last phenomenon is probably the result of the inhibition of phagocytosis of the cancer cells exposing CALR mutant protein by dendritic cells.
</abstract>

Calreticulin (CALR) is a highly conserved multi-function protein that primarily localizes within the lumen of the endoplasmic reticulum (ER). It participates in various processes in the cells, including glycoprotein chaperoning, regulation of Ca2+ homeostasis, antigen processing and presentation for adaptive immune response, cell adhesion/migration, cell proliferation, immunogenic cell death, gene expression and RNA stability. The role of CALR in the assembly, retrieval and cell surface expression of MHC class I molecules is well known. A fraction of the total cellular CALR is localized in the cytosol, following its retro-translocation from the ER. In the cell stress conditions, CALR is also expressed on the cell surface via an interaction with phosphatidylserine localized on the inner leaflet of the plasma membrane. The abovementioned mechanism is relevant for the recognition of the cells, as well as immunogenicity and phagocytic uptake of proapoptotic and apoptotic cells.
Lastly, the presence of CALR exon 9 gene mutations was confirmed in patients with myeloproliferative neoplasms. Their presence results in an abnormal CALR structure due to the loss of its ER-retention sequence, CALR extra-ER localisation, the formation of a complex with thrombopoietin receptor, and oncogenic transformation of hematopoietic stem cells. It is also known that CALR exon 9 mutants are highly immunogenic and induce T cell response. Despite this fact, CALR mutant positive hematopoietic cells emerge. The last phenomenon is probably the result of the inhibition of phagocytosis of the cancer cells exposing CALR mutant protein by dendritic cells.

Calreticulin – a multifaced protein

Department of Hematology and Bone Marrow Transplantation

Postępy Higieny i Medycyny Doświadczalnej

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Kalretikulina – białko o wielu twarzach

Calreticulin (CALR) is a highly conserved multi-function protein that primarily localizes within the lumen of the endoplasmic reticulum (ER). It participates...

Calreticulin – a multifaced protein

Article Category: Review

Published Online: May 18, 2021

Page range: 328 - 336

Received: Jul 02, 2020

Accepted: Nov 24, 2020

DOI: https://doi.org/10.5604/01.3001.0014.8892

Keywords
Calreticulin, oncogenic transformation, immune system escape, myeloproliferative neoplasms

© 2021 Zuzanna Kanduła et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Calreticulin – a multifaced protein

Article Category: Review

Published Online: May 18, 2021

Page range: 328 - 336

Received: Jul 02, 2020

Accepted: Nov 24, 2020

DOI: https://doi.org/10.5604/01.3001.0014.8892

KeywordsCalreticulin, oncogenic transformation, immune system escape, myeloproliferative neoplasms

© 2021 Zuzanna Kanduła et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
Calreticulin, oncogenic transformation, immune system escape, myeloproliferative neoplasms