Retromer
The retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network (TGN).[1][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.[3]
Structure
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, SNX5 and SNX6.[4] 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, and the Wnt receptor Wntless.[5] 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. It is also required for the recycling of the cell surface receptor CED-1, which is necessary for phagocytosis of apoptotic cells.[6]
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.[7]
References
- ^ Seaman MN (2005). "Recycle your receptors with retromer". Trends Cell Biol. 15 (2): 68–75. doi:10.1016/j.tcb.2004.12.004. PMID 15695093.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Pfeffer SR (2001). "Membrane transport: retromer to the rescue". Curr. Biol. 11 (3): R109–11. doi:10.1016/S0960-9822(01)00042-2. PMID 11231171.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Seaman MN, McCaffery JM, Emr SD (1998). "A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast". J. Cell Biol. 142 (3): 665–81. doi:10.1083/jcb.142.3.665. PMC 2148169. PMID 9700157.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wassmer T, Attar N, Bujny MV, Oakley J, Traer CJ, Cullen PJ (2007). "A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer". J. Cell. Sci. 120 (Pt 1): 45–54. doi:10.1242/jcs.03302. PMID 17148574.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Eaton S (2008). "Retromer retrieves wntless". Dev. Cell. 14 (1): 4–6. doi:10.1016/j.devcel.2007.12.014. PMID 18194646.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Chen D, Xiao H, Zhang K, Gao Z, Jian Y, Qi X, Sun J, Miao L, Yang C (2010). "Retromer is required for apoptotic cell clearance by phagocytic receptor recycling". Science. 327 (5970): 1261–4. doi:10.1126/science.1184840. PMID 20133524.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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 (2008). "Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation". Proc. Natl. Acad. Sci. U.S.A. 105 (20): 7327–32. doi:10.1073/pnas.0802545105. PMC 2386077. PMID 18480253.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
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