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Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity

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Summary:Plasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism, growth and response to stress or drugs. In Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that provides a model to dissect the molecular details underlying cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence revealing novel roles of the cytosolic N- and C-termini of Jen1 in its biogenesis, PM stability and transport activity, using functional analyses of Jen1 truncations and chimeric constructs with UapA, an endocytosis-insensitive transporter of Aspergillus nidulans. Our results show that both N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. Importantly, we provide evidence that Jen1 N- and C-termini undergo transport-dependent dynamic intramolecular interactions, which affect the transport activity and turnover of Jen1. Our results support an emerging concept where the cytoplasmic termini of PM transporters control transporter cell surface stability and function through flexible intramolecular interactions with each other. These findings might be extended to other MFS members to understand conserved and evolving mechanisms underlying transporter structure–function relationships.
Main Authors:Barata-Antunes, Cláudia
Other Authors:Talaia, Gabriel; Broutzakis, George; Ribas, David; De Beule, Pieter; Casal, Margarida; Stefan, Christopher J.; Diallinas, George; Paiva, Sandra
Subject:Major facilitator superfamily MFS Transporters Monocarboxylic acids Endocytosis Arrestin Cytosolic termini Protein sorting Protein turnover Substrate specificity Ubiquitylation
Year:2022
Country:Portugal
Document type:article
Access type:open access
Associated institution:Universidade do Minho
Language:English
Origin:RepositóriUM - Universidade do Minho

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