Retromer: Structure, function, and roles in mammalian disease

Retrograde transport from the endosome to the Golgi is mediated by a 5 protein complex known as the retromer. These five proteins (Vps5, Vps17, Vps26, Vps29, and Vps35 in yeast and SNX1/2, SNX5/6, Vps26, Vps29, and Vps35 in mammalian cells) act as a coat for vesicles budding off of the endosome, as well as perform cargo sorting at the endosome. The retromer is well conserved between yeast and mammalian systems, though variations exist within the mammalian retromer. Functionally, the retromer has been linked to prominent neurodegenerative diseases such as Alzheimer's and Parkinson's in human models as well as diabetes mellitus. However, the retromer also plays a role in the virulence of several microbial pathogens. Despite the current understanding of the retromer complex, there are still many questions to be answered in regards to its overall role in cell homeostasis. (C) 2015 Elsevier GmbH. All rights reserved.