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Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
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...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...

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Related Experiment Video

Updated: May 22, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

Trafficking and proteolytic processing of APP.

Christian Haass1, Christoph Kaether, Gopal Thinakaran

  • 1DZNE-German Center for Neurodegenerative Diseases, 80336 Munich, Germany; Adolf Butenandt-Institute, Biochemistry, Ludwig-Maximilians University, 80336 Munich, Germany. christian.haass@dzne.lmu.de

Cold Spring Harbor Perspectives in Medicine
|May 4, 2012
PubMed
Summary

Alzheimer disease involves amyloid beta-peptide deposits. This study details the secretase enzymes that process the amyloid precursor protein, influencing peptide generation and disease progression.

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Related Experiment Videos

Last Updated: May 22, 2026

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
07:55

Imaging the Intracellular Trafficking of APP with Photoactivatable GFP

Published on: October 17, 2015

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
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Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer disease (AD) is characterized by amyloid beta-peptide (Aβ) deposits.
  • Aβ is proteolytically derived from the β-amyloid precursor protein (APP).
  • Secretase enzymes (β-, γ-, and α-secretase) mediate APP processing.

Purpose of the Study:

  • To describe the cell biology and biochemistry of secretases involved in APP processing.
  • To outline APP maturation and trafficking within the secretory pathway.
  • To illuminate how neuronal activity and familial AD mutations impact Aβ generation.

Main Methods:

  • Cell biological characterization of secretase activities.
  • Biochemical analysis of APP processing.
  • Investigating APP trafficking and maturation.
  • Examining the effects of neuronal activity and mutations on Aβ production.

Main Results:

  • Detailed characterization of β-, γ-, and α-secretase functions.
  • Understanding of APP's journey through the secretory pathway.
  • Insights into how secretase activity influences Aβ levels.
  • Demonstration of neuronal activity and genetic mutations affecting Aβ generation.

Conclusions:

  • Secretase activity is central to Aβ generation in Alzheimer disease.
  • APP processing and trafficking are critical determinants of Aβ pathology.
  • Neuronal activity and familial AD mutations modulate Aβ production, impacting disease onset and progression.