The retromer is a complex of protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s that has been shown to be important in recycling transmembrane receptors from endosome

Endosome

In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...

s to the trans-Golgi network

Golgi apparatus

The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....

 (TGN).

Discovery

Retromer was first identified in yeast to mediate VPS10 retrieval from a pre-vacuolar

Vacuole

A vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...

 compartment (yeast endosome equivalent) to the trans-Golgi network in 1998.

Structure

The retromer complex is highly conserved: homologs

Homology (biology)

Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

 have been found in C. elegans

Caenorhabditis elegans

Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

, mouse

Mouse

A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

 and human

Human

Humans are the only living species in the Homo genus...

. The retromer complex consists of 5 proteins in yeast: Vps35p, Vps26p, Vps29p, Vps17p, Vps5p. In mammals it consists of Vps26

VPS26A

Vacuolar protein sorting-associated protein 26A is a protein that in humans is encoded by the VPS26A gene.This gene belongs to a group of vacuolar protein sorting genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport...

, Vps29

VPS29

VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex.-Yeast homolog:The homologous protein in yeast is Vacuolar protein sorting 29 homolog VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the...

, Vps35

VPS35

Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene.This gene belongs to a group of vacuolar protein sorting genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of...

, SNX1

SNX1

Sorting nexin-1 is a protein that in humans is encoded by the SNX1 gene. The protein encoded by this gene is a sorting nexin. SNX1 is a component of the retromer complex.- Function :...

 and possibly SNX2

SNX2

Sorting nexin-2 is a protein that in humans is encoded by the SNX2 gene.-Further reading:...

, SNX5

SNX5

Sorting nexin-5 is a protein that in humans is encoded by the SNX5 gene.This gene encodes a member of the sorting nexin family. Members of this family contain a phox domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking...

 and SNX6

SNX6

Sorting Nexin 6 also known as SNX6 is a well-conserved membrane-associated protein belonging to the sorting nexin family that is a component of the retromer complex. The protein contains a coiled-coil domain at its C terminus and a PX domain at its N terminus. Binding to PIM1 causes translocation...

. It is proposed to act in two subcomplexes: (1) Structural subcomplex composed of SNX1 and possibly SNX2 that acts to bend membranes and form tubules/vesicle

Vesicle (biology)

A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

s and (2) a cargo selective subcomplex that consists of Vps35, Vps26 and Vps29.

Function

The retromer complex has been shown to mediate retrieval of various transmembrane receptors, such as the cation-independent mannose 6-phosphate receptor

Insulin-like growth factor 2 receptor

In the fields of biochemistry and cell biology, the insulin-like growth factor 2 receptor , also called the cation-independent mannose-6-phosphate receptor is a protein that in humans is encoded by the IGF2R gene...

, the functional mammalian counterpart of VPS10, and the Wnt

WNT

WNT is a three-letter abbreviation with multiple meanings, as described below:*Windows NT*WNT *Wnt signaling pathway, a complex protein network...

 receptor Wntless

GPR177

G protein-coupled receptor 177 , commonly known as Wntless, is a human gene that encodes a receptor for Wnt proteins in Wnt-secreting cells.Wntless was recently shown to be a cargo for the retromer complex....

. Retromer is required for the recycling of Kex2p

Kexin

Kexin is a prohormone processing protease found in the budding yeast that shares structural similarities with the bacterial protease subtilisin. It is encoded by the yeast gene KEX2 and usually referred to in the scientific community as Kex2p. The first mammalian homologue of this protein to be...

 and DPAP-A which also cycle between the trans-Golgi network and a pre-vacuolar (yeast endosome equivalent) compartment in yeast. It is also required for the recycling of the cell surface receptor CED-1, which is necessary for phagocytosis of apoptotic cells.

Retromer plays a central role in the retrieval of several different cargo proteins from the endosome to the trans-Golgi network. However, it is clear that there are other complexes and proteins that act in this retrieval process. So far it is not clear whether other components that have been identified in the retrieval pathway act with retromer in the same pathway or are involved in alternative pathways. Recent studies have implicated retromer sorting defects in Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

.