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Related Concept Videos

Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...

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Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration.

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Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.

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TDP-43 dysfunction compromises UPF1-dependent mRNA metabolism in ALS.

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Related Experiment Video

Updated: Jun 5, 2026

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

A cytoplasmic turn in TDP-43 toxicity.

Christopher J Donnelly1

  • 1Department of Neurology, University of Texas Southwestern, Dallas, TX, USA; Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern, Dallas, TX, USA.

Neuron
|June 3, 2026
PubMed
Summary

TDP-43 dysfunction contributes to neurodegenerative diseases. Researchers found that impaired TDP-43 function alters processing body activity, with DCPS identified as a key factor in neurotoxicity.

Area of Science:

  • Neurobiology
  • Molecular Biology
  • Genetics

Background:

  • TDP-43 protein aggregation and dysfunction are hallmarks of neurodegenerative diseases like ALS and FTD.
  • The precise mechanisms linking TDP-43 loss-of-function to neurotoxicity remain incompletely understood.

Purpose of the Study:

  • To investigate the functional consequences of TDP-43 loss-of-function on cellular processes.
  • To identify genetic factors that modify TDP-43-associated neurotoxicity.

Main Methods:

  • Utilized cellular and genetic models to study TDP-43 function and its impact on P-body dynamics.
  • Performed genetic screens to identify modifiers of TDP-43 neurotoxicity.

Main Results:

  • Demonstrated that TDP-43 loss-of-function leads to significant alterations in processing body (P-body) assembly and function.

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Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
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Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

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Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
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Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Published on: November 11, 2014

Related Experiment Videos

Last Updated: Jun 5, 2026

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae
07:14

Optogenetic Phase Transition of TDP-43 in Spinal Motor Neurons of Zebrafish Larvae

Published on: February 25, 2022

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
08:44

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Published on: November 11, 2014

  • Identified the decapping scavenger enzyme DCPS as a novel genetic modifier that exacerbates TDP-43-induced neurotoxicity.

    • Conclusions:

    • TDP-43 plays a critical role in regulating P-body homeostasis.
    • Targeting DCPS may offer a therapeutic strategy for neurodegenerative diseases associated with TDP-43 dysfunction.