Abstract

Nutrient transporters are prominent and ubiquitous components of the plasma membrane in all cell types. Their expression and regulation are tightly linked to the cells’ needs. Environmental factors such as nutrient starvation or osmotic stress prompt an acute remodeling of transporters and the plasma membrane to efficiently maintain homeostasis in cell metabolism. Lateral confinement of nutrient transporters through dynamic segregation within the plasma membrane has recently emerged as an important phenomenon that facilitates spatiotemporal control of nutrient uptake and metabolic regulation. Here, we review recent studies highlighting the mechanisms connecting the function of amino acid permeases with their endocytic turnover and lateral segregation within the plasma membrane. These findings indicate that actively controlled lateral compartmentalization of plasma membrane components constitutes an important level of regulation during acute cellular adaptations.

Highlights

  • Cells are constantly exposed to environmental fluctuations and require rapid adaptations to sustain proper growth and survival

  • Starvation is regulated at the plasma membrane (PM) through a tight remodeling of nutrient transporters, highly abundant and conserved components of the PM in all cells

  • Nutrient transporters at the yeast PM have been shown to segregate into different compartments

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Summary

INTRODUCTION

Cells are constantly exposed to environmental fluctuations and require rapid adaptations to sustain proper growth and survival. The budding yeast Saccharomyces cerevisiae represents a promising model system for the study of such segregation. Both lipids and proteins of the yeast PM exhibit unusually slow lateral diffusion, and they form large domains that can be studied by conventional light microscopy (Spira et al, 2012a). A critical environmental stress that cells constantly face is nutrient limitation. Starvation is regulated at the PM through a tight remodeling of nutrient transporters, highly abundant and conserved components of the PM in all cells. On the one hand, increased transcription and PM delivery of transporters occur when nutrients are scarce. Transcriptional repression and ubiquitindependent internalization prevent excessive substrate uptake when nutrients are abundant. Selective ubiquitination and downregulation of PM transporters are driven by the concerted action of the E3 ubiquitin ligase Rsp and cargo-selective adaptors of the α-arrestin family (Nikko and Pelham, 2009)

Membrane Segregation and Nutrient Transporters
NUTRIENT TRANSPORTER DISTRIBUTION AT THE PLASMA MEMBRANE
DYNAMIC LATERAL RELOCATION THROUGH A CONFORMATIONAL SWITCH
CELLULAR REGULATION OF NUTRIENT TRANSPORTER CLUSTERING
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