Related Experiment Video

Updated: Oct 11, 2025

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking
08:51

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

Published on: February 12, 2022

3.7K

De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal

Kai-En Chen1, Qian Guo1, Timothy A Hill1,2

  • 1Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland 4072, Australia.

Science Advances
|December 1, 2021
PubMed

Insights

Researchers developed novel macrocyclic peptides to study the retromer complex, essential for cell trafficking and implicated in Parkinson's disease. These peptides offer new tools for understanding retromer function and potential therapeutic strategies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • The retromer complex (Vps35-Vps26-Vps29) is crucial for endosomal trafficking and signaling.
  • Dysfunction of retromer, particularly Vps35 mutations, is linked to Parkinson's disease.
  • Pathogens exploit retromer for cellular invasion.

Purpose of the Study:

  • To create high-affinity, specific macrocyclic peptides targeting the retromer complex.
  • To utilize these peptides as molecular tools for probing retromer function and interactions.
  • To explore potential therapeutic applications of retromer-targeting peptides.

Main Methods:

  • Design and synthesis of novel macrocyclic peptides.
  • Biochemical assays to assess peptide binding affinity and specificity.
  • X-ray crystallography to determine peptide-retromer complex structures.
  • Cell-based assays to evaluate peptide effects on retromer function and localization.

Main Results:

  • Developed macrocyclic peptides with high affinity and specificity for the retromer complex.
  • Identified peptide binding modes, with most mimicking known interactors at the Vps29 interface.
  • Discovered a novel peptide (RT-L4) binding the Vps35-Vps26 interface, acting as an effective molecular chaperone.
  • Demonstrated utility of tagged peptides for studying retromer cellular localization and interactions.

Conclusions:

  • Novel macrocyclic peptides provide powerful tools for dissecting retromer function.
  • Peptide RT-L4 represents a promising therapeutic lead for retromer-related disorders.
  • These peptides advance our understanding of endosomal trafficking and Parkinson's disease mechanisms.

More Related Videos

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells11:05

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

9.3K
Visualizing Membrane Ruffle Formation using Scanning Electron Microscopy08:05

Visualizing Membrane Ruffle Formation using Scanning Electron Microscopy

Published on: May 27, 2021

2.8K

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...
4.1K
Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
7.5K
ER Retrieval Pathway01:45

ER Retrieval Pathway

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...
4.0K
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing 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...
12.0K
Recycling Endosomes and Transcytosis00:58

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.9K
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,...
7.9K