The Functional Relationship between the Retromer and Yeast Dynamin at the Endosome

Abstract

Membrane trafficking from the late endosome to the Golgi in cells is termed retrograde transport, essential for recycling of important macromolecules including cell membrane receptors. Retrograde transport is regulated by a family of proteins known as the retromer composed of 5 VPS proteins (Vps5, Vps17, Vps26, Vps29, and Vps35). The retromer acts as the coat proteins for vesicles emerging from late endosomes. Loss of Retromer function has been previously implicated in both Parkinson's and Alzheimer's disease. Vps1, a yeast dynamin-like protein, plays a role in a range of intracellular trafficking pathways necessary for endocytic, secretory, and recycling pathways. Vps1 acts as a scission protein in yeast endocytosis by binding to actin. The retromer and Vps1 are hypothesized to work in concert in the retrograde pathway, with Vps1 acting in a similar manner to its role in endocytosis. We found that Vps1 and retromer colocalize in cells, and both localize to the endosome in yeast. Functionally, Vps1 and retromer component protein Vps35 exhibit evidence of a genetic relationship. Though Vps1 displays no ability to bind to individual retromer components in vivo,double deletion of Vps1 and retromer componentsresults in more severe defects in Vps10 receptor trafficking when compared with cells lacking Vps1 or retromer components.