Related Experiment Video
Updated: Jul 11, 2026
09:37
An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Identification of a postendocytic sorting sequence in CCR5
Maurine Delhaye1, Audrey Gravot, Diana Ayinde
1Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche 8104), Paris, France.
Molecular Pharmacology
|September 15, 2007
Summary
The chemokine receptor 5 (CCR5) is crucial for HIV-1 entry. A specific C-terminal sequence regulates its recycling, offering new therapeutic targets for HIV-1 infection.
Area of Science:
- Cell Biology
- Virology
- Molecular Biology
Background:
- Chemokine receptor 5 (CCR5) is a G protein-coupled receptor (GPCR) essential for HIV-1 entry.
- CCR5 is a primary target for antiviral therapies aimed at blocking HIV-1 entry.
- Mechanisms governing CCR5 intracellular trafficking remain largely unelucidated.
Purpose of the Study:
- To investigate the role of CCR5 molecular determinants in its post-endocytic trafficking.
- To understand how CCR5 cell surface expression is regulated for HIV-1 entry inhibition.
Main Methods:
- Constructed progressive deletion mutants of the CCR5 C-terminal domain.
- Stably expressed CCR5 mutants in HEK293 cells.
- Analyzed receptor internalization, recycling, and degradation pathways.
Main Results:
- All CCR5 deletion mutants were expressed at the cell surface and functioned as HIV-1 receptors.
- Internalized mutants failed to recycle and were directed to lysosomal degradation.
- A four-amino-acid sequence at the C terminus was identified as essential for CCR5 recycling, acting as a PDZ-interacting motif.
Conclusions:
- The CCR5 cytoplasmic domain contains a recycling signal similar to those in other GPCRs.
- This PDZ-interacting sequence is critical for CCR5 recycling.
- Targeting CCR5's recycling pathway presents a potential therapeutic strategy against HIV-1.
More Related Videos
Related Concept Videos
01:41Signal Sequences and Sorting Receptors
Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
01:34Directing 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...
01:25Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
01:28The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
01:45ER 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...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
00:58Recycling 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...
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...