Related Experiment Video
Updated: May 13, 2026
12:44
Electrophoretic Mobility Shift Assay (EMSA) for the Study of RNA-Protein Interactions: The IRE/IRP Example
Published on: December 3, 2014
Prion protein regulates iron transport by functioning as a ferrireductase
Ajay Singh1, Swati Haldar, Katharine Horback
1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Journal of Alzheimer'S Disease : JAD
|March 13, 2013
Summary
The prion protein (PrPC) acts as a ferrireductase, crucial for iron absorption and metabolism. Its absence leads to systemic iron deficiency and cellular iron uptake issues, impacting iron balance in neurodegenerative diseases.
Area of Science:
- Biochemistry
- Neuroscience
- Cell Biology
Background:
- The normal function of prion protein (PrPC) remains largely unknown despite its association with prion disorders.
- Understanding PrPC's role is critical for deciphering the molecular mechanisms underlying neurodegeneration and systemic iron regulation.
Purpose of the Study:
- To elucidate the physiological function of PrPC.
- To investigate the role of PrPC in iron metabolism and its implications for iron homeostasis.
Main Methods:
- Utilized PrP knock-out (PrP-/-) and wild-type (PrP+/+) mice to study iron absorption and distribution.
- Employed radioactive iron (59FeCl3) uptake studies in vivo and in cultured macrophages and neuroblastoma cells.
- Assessed PrPC's ferrireductase activity in neuroblastoma cells expressing PrPC.
Main Results:
- PrP-/- mice exhibit systemic iron deficiency and impaired cellular iron uptake and storage, particularly of non-transferrin-bound iron.
- PrPC functions as a ferrireductase (FR), with activity dependent on its copper-binding region and membrane localization.
- Iron imbalance in PrP-/- mice is partially corrected by excess iron but recurs upon withdrawal, indicating a fundamental defect in iron metabolism.
Conclusions:
- PrPC is a ferrireductase essential for cellular iron uptake and systemic iron homeostasis.
- Dysfunctional PrPC contributes to iron dysregulation observed in prion diseases like sporadic-Creutzfeldt-Jakob disease.
Related Concept Videos
01:28The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
01:29Protein Folding Quality Check in the RER
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...