Ubiquitination and Membrane Protein Trafficking in Yeast

Ubiquitination serves as a pivotal post-translational modification that governs the fate of plasma membrane proteins in the budding yeast Saccharomyces cerevisiae. Attachment of ubiquitin moieties to specific lysine residues of transporters and receptors marks them for internalisation and subsequent delivery to the vacuole for degradation or recycling. This sorting process relies on the concerted action of E3 ubiquitin ligases—principally Rsp5—and a family of adaptor proteins known as α-arrestins, which bridge cargo and ubiquitin ligase. Under changing environmental conditions, such as nutrient availability or proteotoxic stress, selective ubiquitination ensures rapid removal of obsolete or damaged membrane proteins, while permitting the insertion of alternative transporters via the secretory pathway. The molecular choreography involves recognition of phosphorylation signals on adaptor proteins, adaptor recruitment to the plasma membrane or trans-Golgi network, ubiquitin conjugation, clathrin-mediated endocytosis and, ultimately, vacuolar trafficking. Together, these processes maintain cellular homeostasis, modulate metabolic flux and orchestrate responses to external stimuli. Beyond yeast, the principles of ubiquitin-dependent membrane protein turnover are conserved in higher eukaryotes, underscoring their broad biological significance and potential applications in biotechnology and medicine.

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Ubiquitination and Membrane Protein Trafficking in Yeast publication trend

The graph below shows the total number of articles in ubiquitination and membrane protein trafficking in yeast across all publications each year (not limited to Nature Index journals).

Technical terms

Ubiquitination: Covalent attachment of the small protein ubiquitin to lysine residues of a substrate, marking it for endocytosis or degradation.

α-Arrestin: A family of adaptor proteins that bind membrane cargo and recruit the ubiquitin ligase Rsp5 to facilitate selective ubiquitination.

Rsp5 ubiquitin ligase: A HECT-domain E3 enzyme in yeast responsible for transferring ubiquitin to target proteins during trafficking and quality control.

Endocytosis: The process by which cells internalise plasma membrane proteins into vesicles for sorting to the vacuole or recycling pathways.

Vacuole: A lytic compartment in yeast analogous to the lysosome, where internalised cargo is degraded or stored.

References

1. The Yeast Permease Agp2 Senses Cycloheximide and Undergoes Degradation That Requires the Small Protein Brp1-Cellular Fate of Agp2 in Response to Cycloheximide. International Journal of Molecular Sciences (2023).
2. The α‐arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis. Biology of the Cell (2021).
3. The ART-Rsp5 ubiquitin ligase network comprises a plasma membrane quality control system that protects yeast cells from proteotoxic stress. eLife (2013).
4. Ubiquitination Mediated by the Npi1p/Rsp5p Ubiquitin-protein Ligase Is Required for Endocytosis of the Yeast Uracil Permease (∗). Journal of Biological Chemistry (1996).