Related Experiment Video
Updated: Jun 14, 2025
09:16
Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
7.5K
Episodic Transport of Protein Aggregates Achieves a Positive Size Selectivity in Aggresome Formation
Biorxiv : the Preprint Server for Biology
|August 30, 2024
Summary
Cells sequester toxic protein aggregates into aggresomes via microtubule-organizing center (MTOC) transport. This study reveals dynein motor proteins selectively transport larger aggregates, a mechanism crucial for aggresome formation and protein quality control.
Area of Science:
- Cell Biology
- Molecular Biology
- Biophysics
Background:
- Eukaryotic cells utilize protein quality control pathways to manage misfolded proteins.
- Aggregated proteins are directed to selective autophagy or sequestered into aggresomes at the microtubule-organizing center (MTOC).
- The precise mechanism of selective aggregate sequestration into aggresomes is not fully understood.
Purpose of the Study:
- To elucidate the mechanism of MTOC-directed transport of protein aggregates.
- To investigate the factors influencing selective sequestration into aggresomes.
Main Methods:
- Reconstitution of MTOC-directed aggregate transport in Xenopus laevis egg extract.
- Utilized a chemically inducible aggregation system (AgDD).
- Employed high-resolution single-particle tracking and developed a mechanistic model.
Main Results:
- Dynein-mediated transport of protein aggregates is episodic.
- Transport velocity is positively correlated with aggregate size.
- A mechanistic model indicates recurrent dynein complex formation biases larger aggregates for active transport, overcoming viscosity.
- Episodic transport and size selectivity depend on aggresome-dynein adaptors.
Conclusions:
- Aggresome formation involves size-selective, dynein-mediated transport of protein aggregates.
- The findings clarify the mechanism by which larger aggregates are preferentially sequestered.
- Perturbation of aggresome-dynein adaptors disrupts aggresome formation and reverses size selectivity.
Related Concept Videos
01:45Overview of Protein Sorting and Transport
11.2K
Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
11.2K
01:32Export of Misfolded Proteins out of the ER
3.5K
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...
3.5K
03:03Amyloid Fibrils
9.3K
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,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.3K
01:27Post-translational Translocation of Proteins to the RER
5.6K
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...
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...
5.6K
01:45ER Retrieval Pathway
3.8K
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.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
01:34Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K