Signals and mechanisms of endocytosis of eukaryotic lactate transporters

Abstract

Eukaryotic cells internalize or recycle their plasma membrane proteins by endocytosis in response to physiological or stress signals imposed by a changing environment. Defects in membrane cargo trafficking lead to protein mislocalization and activation of turnover pathways, which can result into cellular stress and is often related to human diseases. The α-arrestins connect signalling pathways triggered by external stimuli to the endocytosis of specific plasma membrane transporters or receptors. The Saccharomyces cerevisiae lactate transporter Jen1p has been used as a model membrane cargo protein for elucidating aspects of the mechanisms that control the endocytic turnover of specific transporters in response to the presence of glucose. Here, we discover a novel pathway of Jen1p endocytosis and provide further insights on how particular α-arrestins mediate the ubiquitylation of transporters under distinct physiological conditions (presence of cycloheximide or prolonged growth in lactate).