Multiple nutrient transporters enable cells to mitigate a rate-affinity tradeoff.

Area of Science:

• Molecular Biology
• Biophysics
• Systems Biology

Background:

• Eukaryotic genomes frequently encode multiple transporters for identical nutrients, such as the 17 hexose transporters (HXTs) in budding yeast for glucose transport.
• Cellular nutrient uptake is crucial for survival and is mediated by various transport mechanisms, including facilitated diffusion and symport.

Purpose of the Study:

• To investigate the rate-affinity tradeoff in nutrient transporters and its implications for cellular nutrient uptake.
• To determine if cells utilize multiple transporters to mitigate this tradeoff under different nutrient concentrations.

Main Methods:

• Mathematical modeling was employed to analyze the relationship between transport rate, affinity, and import flux.
• Fluorescent tagging of seven HXT genes in budding yeast was used to monitor transporter expression dynamics.
• Experimental data on HXT gene expression was compared with known transporter affinities.

Main Results:

• Mathematical models predicted a non-monotonic relationship between transporter characteristics and import flux, with optimal transporters for specific nutrient concentrations.
• Transporter regulation in budding yeast, particularly HXT gene expression in response to falling glucose levels, aligns with the predicted rate-affinity tradeoff.
• The order of transporter expression as glucose levels decrease generally follows their affinity for glucose, supporting the tradeoff hypothesis.

Conclusions:

• The rate-affinity tradeoff is a significant constraint in the evolution of nutrient transporters.
• Cells can strategically employ multiple transporters with varying affinities to optimize nutrient import across diverse environmental conditions.
• This study provides evidence for a common evolutionary tradeoff in cellular nutrient transport mechanisms.