Some plasma membrane sensor proteins that detect nutrients look a lot like the transporters that move those small molecules across the membrane. On page 327, Wu et al. present a model suggesting that the sensors work like them, too—minus the transport step.
Previous work showed that a single mutation in the Ssy1p amino acid sensor increased its basal signaling level and made it hyperresponsive to extracellular ligand. Starting from those data, the team developed a model of how the sensor might control transcriptional activation of amino acid transporters.
According to the model, the sensor could sit in the membrane with its ligand-binding site facing the intracellular or extracellular space. In its unbound state, the sensor freely flips between inside- and outside-facing conformations. But ligand freezes the sensor in one conformation or the other so it cannot readily shift between the two sides of the membrane. Transporters, by contrast, do their job by flipping their ligand binding site from one side of the membrane to the other when ligand is bound.
When the sensor is facing the outside of the cell, it initiates signaling. If the model were correct, then increased levels of intracellular amino acids should inhibit signaling. When the team tested this by raising the levels of intracellular leucine, they found that Ssy1p signaling was inhibited.
By converting the extracellular and intracellular nutrient concentrations into a regulated signaling pathway, Ssy1p may better control nutrient homeostasis. Now the question is whether the model can be generalized to other sensors, such as those that detect glucose.