Cell surface recycling in yeast: mechanisms and machineries

Abstract

Sorting internalized proteins and lipids back to the cell surface controls the supply of molecules throughout the cell and regulates integral membrane protein activity at the surface. One central process in mammalian cells is the transit of cargo from endosomes back to the plasma membrane (PM) directly, along a route that bypasses retrograde movement to the Golgi. Despite recognition of this pathway for decades we are only beginning to understand the machinery controlling this overall process. The budding yeastSaccharomyces cerevisiae, a stalwart genetic system, has been routinely used to identify fundamental proteins and their modes of action in conserved trafficking pathways. However, the study of cell surface recycling from endosomes in yeast is hampered by difficulties that obscure visualization of the pathway. Here we briefly discuss how recycling is likely a more prevalent process in yeast than is widely appreciated and how tools might be built to better study the pathway.

Keywords: cell surface recycling; deubiquitination; endocytosis; yeast.

Figure 1. Endosomal trafficking pathways

Internalized cell surface membrane proteins move to a common, early endosome. Cargo proteins localized to endosomes follow several distinct trafficking pathways: including the ubiquitin-mediated degradation pathway to the lysosome; the retrograde pathway to the Golgi; and the recycling pathway back to the plasma membrane. Trafficking within these broad directional classes of transit can be further subcategorized and there is significant overlap between each pathway.

Figure 2. Ubiquitination status of cargo as an endosomal trafficking determinant

Schematic representation of the counteracting activity between Ub-ligases and deubiquitinating enzymes (DUbs), the balance of which dictates directional trafficking through the endolysosomal system. The R-SNARE protein Snc1 labelled with GFP serves as a useful example, as it exhibits steady state localization at the plasma membrane, cycling between early endosomes and the cell surface in an Rcy1 dependent manner (left). However, Snc1 can also undergo ubiquitination and sort to the vacuole, which occurs very efficiently when cells are cultured beyond late log phase (right).