Retromer
Retromer is a multiprotein complex that acts to sort and traffic cargo from endosomes to the trans-Golgi network or to the cell surface. By mediating the localisation of many membrane proteins, the activity of the retromer complex has been linked to processes such as lysosome biogenesis, and aspects of metazoan development[1]. Additionally, retromer-mediated transport has been implicated in a growing number of neurological diseases, but was first linked to Alzheimer’s disease (AD). The neuronal retromer traffics the amyloid-precursor protein (APP) away from endosomes, a site where APP is cleaved into pathogenic fragments in Alzheimer’s disease. It has been hypothesized that deficiencies in specific vacuolar protein sorting’ (VPS) proteins that build up the retromer complex, are important for mediating the trafficking and pathogenic processing of APP[2].
[1] M.N. Seaman. The retromer complex - endosomal protein recycling and beyond. J Cell Sci. 2012 Oct 15;125(Pt 20):4693-702.
[2] V.J. Mecozzi et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nat Chem Biol. 2014 Jun;10(6):443-9.