Eisosomal Biology in Yeast Systems

Eisosomes are furrow-like invaginations of the yeast plasma membrane that form stable microdomains scaffolded by BAR-domain proteins Pil1 and Lsp1. These structures compartmentalise specific lipids—such as phosphatidylinositol 4,5-bisphosphate, sterols and sphingolipids—and sequester a subset of transporters and signalling proteins. By modulating membrane curvature and tension, eisosomes act as mechanosensitive platforms that regulate membrane homeostasis, endocytic site selection and nutrient transporter retention. They also participate in stress responses by protecting cargoes from degradation, organising lipid metabolism and coordinating adaptive signalling pathways. Recent work has unveiled dynamic behaviours of the eisosomal lattice, its influence on downstream kinases, and its role in metabolic regulation, highlighting its centrality to yeast physiology and its emerging potential as a model for lateral membrane organisation in eukaryotes.

Research from Nature Portfolio

Recent structural analyses have isolated near-native eisosomal assemblies as helical tubules bound by Pil1/Lsp1. High-resolution cryo-EM reconstructions reveal a lattice that selectively sequesters PI(4,5)P₂, phosphatidylserine and sterols beneath its coat. Molecular dynamics and variability analyses demonstrate that stretching of the BAR-domain lattice liberates these lipids, providing a mechanistic basis for membrane tension sensing.

Investigations into signalling crosstalk show that activation of the cell wall integrity pathway impedes eisosome disassembly under plasma membrane stress. By blocking the release of the Slm1 regulator from eisosomes, this pathway negatively regulates TORC2-Ypk1/2 signalling, ensuring a balanced response to cell wall damage and preserving membrane compartment integrity.

High-resolution fluorescence microscopy has elucidated how steric exclusion and protein conformation govern transporter localisation within eisosomal domains. Integral membrane proteins with large cytoplasmic regions are passively excluded, while others are conditionally trapped at eisosomal edges. Substrate binding triggers conformational changes that release transporters from the microdomain, illustrating how lateral diffusion constraints and dynamic trapping shape plasma membrane organisation.

Eisosomal Biology in Yeast Systems publication trend

The graph below shows the total number of articles in eisosomal biology in yeast systems across all publications each year (not limited to Nature Index journals).

Technical terms

Eisosome: A stable, furrow-like invagination of the yeast plasma membrane formed by BAR-domain proteins, defining a specialised membrane microdomain.

BAR domain: A curved protein motif that binds to lipid bilayers and induces or stabilises membrane curvature, central to eisosome assembly.

Microdomain: A laterally segregated region of the plasma membrane enriched in specific lipids and proteins, performing distinct cellular functions.

Quiescence: A reversible, non-dividing state characterised by metabolic adjustments for survival under nutrient limitation or stress.

Ferroptosis: A regulated form of cell death driven by iron-dependent lipid peroxidation, counteracted by antioxidant mechanisms in the membrane.

Phosphorylation: The reversible addition of a phosphate group to a protein, modulating its activity, interactions and localisation.

References

1. Cryo-EM architecture of a near-native stretch-sensitive membrane microdomain. Nature (2024).
2. Activation of the cell wall integrity pathway negatively regulates TORC2-Ypk1/2 signaling through blocking eisosome disassembly in Saccharomyces cerevisiae. Communications Biology (2024).
3. Steric exclusion and protein conformation determine the localization of plasma membrane transporters. Nature Communications (2018).
4. Ferroptosis-protective membrane domains in quiescence. Cell Reports (2023).
5. Tetraspanner‐based nanodomains modulate BAR domain‐induced membrane curvature. EMBO Reports (2023).
6. The phosphatase Glc7 controls eisosomal response to starvation via posttranslational modification of Pil1. Journal of Cell Science (2023).