Related Experiment Video
Updated: Aug 20, 2025

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions
Published on: June 7, 2020
Calreticulin mutations affect its chaperone function and perturb the glycoproteome
Patrick M Schürch1, Liliana Malinovska2, Mohammad Hleihil3
1Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Abstract:
Calreticulin (CALR) is an endoplasmic reticulum (ER)-retained chaperone that assists glycoproteins in obtaining their structure. CALR mutations occur in patients with myeloproliferative neoplasms (MPNs), and the ER retention of CALR mutants (CALR MUT) is reduced due to a lacking KDEL sequence. Here, we investigate the impact of CALR mutations on protein structure and protein levels in MPNs by subjecting primary patient samples and CALR-mutated cell lines to limited proteolysis-coupled mass spectrometry (LiP-MS). Especially glycoproteins are differentially expressed and undergo profound structural alterations in granulocytes and cell lines with homozygous, but not with heterozygous, CALR mutations. Furthermore, homozygous CALR mutations and loss of CALR equally perturb glycoprotein integrity, suggesting that loss-of-function attributes of mutated CALR chaperones (CALR MUT) lead to glycoprotein maturation defects. Finally, by investigating the misfolding of the CALR glycoprotein client myeloperoxidase (MPO), we provide molecular proof of protein misfolding in the presence of homozygous CALR mutations.
More Related Videos
Related Concept Videos
Protein Folding Quality Check in the RER
Export of Misfolded Proteins out of the ER
Regulation of the Unfolded Protein Response
The Unfolded Protein Response
Molecular Chaperones and Protein Folding
The...
Post-translational Translocation of Proteins to the RER
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...

