Membrane trafficking of yeast transporters: mechanisms and physiological control of downregulation

Abstract

Of the 125 plasma membrane transporters thus far identified in the yeast S. cerevisiae, a growing number is reported to be subject to tight control at membrane trafficking level, in addition to control at transcriptional level. Typical physiological conditions inducing these controls include changes of substrate concentration and availability of alternative nutrients. These changes of conditions often provoke the downregulation of specific transporters eventually accompanied by upregulation of others, which are more appropriate for the new conditions. Downregulation generally involves the onset or acceleration of endocytosis of the transporter and subsequent targeting to the vacuole where it is degraded. In many cases, the same physiological signals also induce diversion of the neosynthesized transporter from the Golgi apparatus to the endosomal/vacuolar degradation pathway without passing through the plasma membrane. In the present review, we first describe the main factors – including the ubiquitin ligase Rsp5p and its partners – involved in downregulation of yeast transporters, at endocytosis and endosomal/vacuolar targeting steps. We then summarize the wide variety of physiological situations reported to induce the downregulation of specific yeast transporters. Finally, we discuss possible mechanisms responsible for a specific transporter to be ubiquitylated and downregulated only under particular conditions. Evidence is accumulating that these mechanisms involve association of the protein with specific lipid environments, possible phosphorylation by protein kinases, and specific binding of the transporter to its own substrates.