Retromer

The retromer is a complex of proteins and has been shown to be important in recycling transmembrane receptors from endosomes to the "trans"-Golgi network (TGN).cite journal | author = Seaman MN | title = Recycle your receptors with retromer | journal = Trends Cell Biol. | volume = 15 | issue = 2 | pages = 68–75 | year = 2005 | month = February | pmid = 15695093 | doi = 10.1016/j.tcb.2004.12.004 | url = ] cite journal | author = Pfeffer SR | title = Membrane transport: retromer to the rescue | journal = Curr. Biol. | volume = 11 | issue = 3 | pages = R109–11 | year = 2001 | month = February | pmid = 11231171 | url = | doi = 10.1016/S0960-9822(01)00042-2 ]

Discovery

Retromer was first identified in yeast to mediate VPS10 retrieval from a pre-vacuolar compartment (yeast endosome equivalent) to the "trans"-Golgi network in 1998.cite journal | author = Seaman MN, McCaffery JM, Emr SD | title = A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast | journal = J. Cell Biol. | volume = 142 | issue = 3 | pages = 665–81 | year = 1998 | month = August | pmid = 9700157 | pmc = 2148169 | url = | doi = 10.1083/jcb.142.3.665 ]

tructure

The retromer complex is highly conserved: homologs have been found in "C. elegans", mouse and human. The retromer complex consists of 5 proteins in yeast: Vps35p, Vps26p, Vps29p, Vps17p, Vps5p. In mammals it consists of Vps26, Vps29, Vps35, SNX1 and possibly SNX2. 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/vesicles 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, the functional mammalian counterpart of VPS10. In addition, retromer is required for the recycling of Kex2p and DPAP-A which also cycle between the "trans"-Golgi network and a pre-vacuolar (yeast endosome equivalent) compartment in yeast.

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.cite journal | author = Muhammad A, Flores I, Zhang H, Yu R, Staniszewski A, Planel E, Herman M, Ho L, Kreber R, Honig LS, Ganetzky B, Duff K, Arancio O, Small SA | title = Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 105 | issue = 20 | pages = 7327–32 | year = 2008 | month = May | pmid = 18480253 | pmc = 2386077 | doi = 10.1073/pnas.0802545105 | url = ]

References