Abstract
The endoplasmic reticulum (ER) performs key cellular functions including protein synthesis, lipid metabolism and signaling. While these functions are spatially isolated in structurally distinct regions of the ER, there is cross-talk between the pathways. One vital player that is involved in ER function is the ER-resident protein calreticulin (CALR). It is a calcium ion-dependent lectin chaperone that primarily assists in glycoprotein synthesis in the ER as part of the protein quality control machinery. CALR also buffers calcium ion release and mediates other glycan-independent protein interactions. Mutations in CALR have been reported in a subset of chronic blood tumors called myeloproliferative neoplasms. The mutations consist of insertions or deletions in the CALR gene that all cause a + 1 bp shift in the reading frame and lead to a dramatic alteration of the amino acid sequence of the C-terminal domain of CALR. This alters CALR function and affects cell homeostasis. This chapter will discuss how CALR and mutant CALR affect ER health and disease.
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Abbreviations
- ATF6:
-
Activating factor 6
- CALR:
-
Calreticulin
- CALR-FS:
-
Frameshift
- CNX:
-
Calnexin
- CTD:
-
C-terminal domain
- ER:
-
Endoplasmic reticulum
- ERAD:
-
ER-Associated degradation
- ERES:
-
ER exit sites
- ERGIC:
-
ER-Golgi intermediate compartments
- ET:
-
Essential thrombocythemia
- GPI:
-
Glycosylphosphatidylinositol
- IRE1:
-
Inositol-requiring enzyme 1
- JAK2:
-
Janus kinase 2
- MHC-I:
-
Major histocompatibility complex I
- MPL:
-
Myeloproliferative leukemia virus oncogene
- MPN:
-
Myeloproliferative neoplasms
- MPO:
-
Myeloperoxidase
- PERK:
-
PKR-like endoplasmic reticulum kinase
- PLC:
-
Peptide loading complex
- PMF:
-
Primary myelofibrosis
- PV:
-
Polycythemia vera
- RAV:
-
Ribosome-associated vesicles
- RER:
-
Rough endoplasmic reticulum
- SER:
-
Smooth endoplasmic reticulum
- SOCE:
-
Store-operated Ca2+ entry
- SREBP:
-
Sterol regulatory-element binding protein
- STAT:
-
Signal transducer and activator of transcription
- STIM1:
-
Stromal interaction molecule 1
- TAP:
-
Transporter associated with antigen processing
- UPR:
-
Unfolded protein response
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Acknowledgments
The cited work from this laboratory was funded by the National Institutes of Health (R01-AI09726). We thank the members of the Cresswell laboratory for valuable discussions.
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Arshad, N., Cresswell, P. (2021). Impact of Calreticulin and Its Mutants on Endoplasmic Reticulum Function in Health and Disease. In: Agellon, L.B., Michalak, M. (eds) Cellular Biology of the Endoplasmic Reticulum . Progress in Molecular and Subcellular Biology, vol 59. Springer, Cham. https://doi.org/10.1007/978-3-030-67696-4_8
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