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Related Concept Videos

Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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...
Cytoplasm01:16

Cytoplasm

The cytoplasm consists of organelles and a framework of protein scaffolds called the cytoskeleton suspended in an aqueous solution, the cytosol. The cytosol is a rich broth of water, ions, salts, and various organic molecules.
Protein Folding and Misfolding
The cytoplasm is the location for several cellular processes, including protein synthesis and folding. The aqueous nature of the cytosol promotes protein folding such that the hydrophobic amino acid side chains are buried in the protein...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.

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Related Experiment Video

Updated: May 9, 2026

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions
06:55

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions

Published on: June 7, 2020

Functional relationships linking C99/APP-βCTF dimerization, proteostasis disruption, and organelle dysfunction.

Céline Badot1, Anaïs Bini1, Eric Duplan1

  • 1Université Côte d'Azur, CNRS UMR7275, INSERM U1323, Institute of molecular and cellular pharmacology, Laboratory of Excellence (LABEX) DistALZ, 660 route des Lucioles, Sophia-Antipolis, Valbonne, 06560, France.

Cell Communication and Signaling : CCS
|May 7, 2026
PubMed
Summary
This summary is machine-generated.

C99 dimerization disrupts cellular proteostasis and organelle function, impacting Alzheimer's disease pathology. This dimerization is influenced by proteasome activity and affects the endosomal-lysosomal-autophagic network.

Keywords:
AggresomesAutophagyBiFCC99 dimerizationC99 dimerization mutantEndosome-lysosome-autophagy compartmentsGolgi fragmentationSmall extracellular vesiclesUbiquitin-proteasome

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Last Updated: May 9, 2026

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Published on: June 7, 2020

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Quantitative Approaches for Studying Cellular Structures and Organelle Morphology in Caenorhabditis elegans
08:47

Quantitative Approaches for Studying Cellular Structures and Organelle Morphology in Caenorhabditis elegans

Published on: July 5, 2019

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Amyloid precursor C99 accumulates in Alzheimer's disease and may cause toxicity independent of amyloid-beta.
  • C99's role in the endosomal-lysosomal-autophagic (ELA) network and its dimerization toxicity are largely unknown.

Purpose of the Study:

  • To investigate the intracellular sites and cellular consequences of C99 dimerization.
  • To elucidate the relationship between C99 dimerization, proteostasis, and organelle function.

Main Methods:

  • Developed a bimolecular fluorescence complementation (BiFC) probe to visualize C99 dimerization and trafficking.
  • Utilized a dimerization mutant (C99G29L/G33L) and wildtype C99 for comparative analysis.
  • Assessed dimer localization, expression, and toxicity in transfected HeLa cells via Western blot and immunocytochemistry.

Main Results:

  • C99 dimers were detected in the Trans-Golgi Network (TGN), with dimerization influenced by proteasomal activity.
  • C99 dimerization negatively impacted the ubiquitin-proteasome system (UPS) and TGN, leading to aggresome formation and Golgi fragmentation.
  • Dimerization induced lysosome repositioning and accumulation of autophagy vesicles, confirming a link between proteostasis and C99 dimerization.

Conclusions:

  • Cellular UPS, autophagy, and γ-secretase activities regulate C99 levels and dimerization.
  • C99 dimerization disrupts proteostasis and organelle function, indicating a bidirectional relationship.
  • Findings highlight C99 dimerization as a key factor in Alzheimer's disease-related cellular dysfunction.