Signals and mechanisms of endocytosis of eukaryotic lactate transporters

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).The strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) and the project PTDC/BIAMIC/5184/2014 funded by national funds through the FCT I.P. and by the ERDF through the COMPETE 2020 - Programa Operacional Competitividade e Internacionalização (POCI); This work is a result of the project EcoAgriFood: Innovative green products and processes to promote Agri-Food BioEconomy" (operação NORTE-01-0145-FEDER-000009), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). GT acknowledges FCT for the SFRH/BD/86221/2012 PhD grant.