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Related Concept Videos

Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

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ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
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ER Retrieval Pathway01:45

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In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
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Role of ER in the Secretory Pathway01:17

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Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
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Smooth Endoplasmic Reticulum01:21

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Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
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Export of Misfolded Proteins out of the ER01:32

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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells
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Calreticulin-Enigmatic Discovery.

Gillian C Okura1, Alamelu G Bharadwaj1, David M Waisman1,2

  • 1Department of Pathology, Dalhousie University, Halifax, NS B3H 1X5, Canada.

Biomolecules
|July 27, 2024
PubMed
Summary
This summary is machine-generated.

This study challenges the long-held belief that calreticulin (CRT) is the high-affinity Ca2+-binding protein (HACBP) of the sarcoplasmic reticulum. Proteomic analyses consistently fail to detect HACBP or CRT in skeletal muscle SR, suggesting the identity is a scientific myth.

Keywords:
Michalakcalregulincalreticulincalsequestrinendoplasmic reticulumessential thrombocythemiahigh-affinity calcium-binding protein (HACBP)sarcoplasmic reticulum

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Calreticulin (CRT) is an intrinsically disordered, multifunctional protein with crucial intracellular and extracellular roles.
  • The widely accepted hypothesis posits that CRT was identified as the sarcoplasmic reticulum's (SR) high-affinity Ca2+-binding protein (HACBP) in 1974.
  • This long-standing assumption has been deeply embedded in scientific literature without rigorous validation.

Observation:

  • A comprehensive reexamination of proteomic analyses of purified SR preparations and components was conducted.
  • Studies analyzed purified SR, longitudinal tubules, and junctional terminal cisternae.
  • These proteomic analyses consistently failed to detect HACBP or CRT in skeletal muscle SR.

Findings:

  • The existence of HACBP has not been reproducible in skeletal muscle SR proteomic studies.
  • Evidence supporting the identity of HACBP and CRT in skeletal muscle SR is lacking.
  • The proposed identity between HACBP and CRT is a non sequitur based on current data.

Implications:

  • The established dogma linking HACBP and CRT in skeletal muscle SR requires reevaluation.
  • This finding necessitates a revision of our understanding of calcium regulation within the SR.
  • Future research should focus on identifying the true HACBP of the SR and clarifying CRT's specific roles in this organelle.