retromer complex

Definition

Target type: cellularcomponent

A conserved hetero-pentameric membrane-associated complex involved in retrograde transport from endosomes to the Golgi apparatus. The budding yeast retromer comprises Vps35p, Vps29p, Vps26p, Vps5p, and Vps17p. The mammalian complex shows slight variation in composition compared to yeast, and comprises SNX1 or SNX2, SNX5 or SNX6, VPS26A or VPS26B, VPS29, and VPS35. [GOC:bf, PMID:26220253, PMID:27385586, PMID:9700157]

The retromer complex is a multi-protein complex that plays a crucial role in intracellular trafficking, specifically in the retrieval of transmembrane receptors and other cargo proteins from the endosomal compartment back to the trans-Golgi network (TGN). It is comprised of three core subunits:
- **VPS26** (vacuolar protein sorting 26), a sorting nexin that binds to the cargo and interacts with other retromer subunits.
- **VPS29**, another sorting nexin that provides a scaffold for the complex and interacts with the VPS35 subunit.
- **VPS35**, a protein that interacts with the cargo and the VPS26 and VPS29 subunits.
This core complex is responsible for recognizing and binding to cargo proteins destined for retrieval.
Additionally, two accessory proteins, **SNX1** and **SNX2**, contribute to the function of retromer by promoting membrane association and cargo sorting.
The retromer complex associates with specific membrane domains through its interaction with phosphoinositides, particularly PI(3)P. This interaction is crucial for the recruitment of the complex to the endosomal membranes and its subsequent cargo sorting activity.
The retromer complex then sorts cargo proteins into transport vesicles that bud from endosomes and move towards the TGN.
This retrieval process is essential for maintaining the appropriate localization and function of various cellular components, including:
- **Transmembrane receptors:** The retromer complex ensures that receptors involved in signaling pathways, such as the Wnt pathway, are recycled back to the cell surface after endocytosis.
- **Lysosomal hydrolases:** The retromer complex helps retrieve lysosomal enzymes from the endosomes, ensuring their proper delivery to lysosomes.
- **Other proteins:** The retromer complex is also involved in the trafficking of other proteins, such as those involved in nutrient transport and cell adhesion.
Dysfunction of the retromer complex is associated with a number of human diseases, including neurodegenerative disorders, such as Alzheimer's disease, and lysosomal storage disorders.
Therefore, the retromer complex plays a critical role in maintaining cellular homeostasis and its proper function is essential for normal cellular processes.'
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Proteins (1)

Compounds (3)