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

Barata-Antunes, Cláudia; Talaia, Gabriel; Broutzakis, George; Ribas, David; De Beule, Pieter; Casal, Margarida; Stefan, Christopher J; ... Paiva, Sandra; + view all (2022) Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity. Journal of Cell Science , 135 (10) , Article 260059. 10.1242/jcs.260059. Green open access

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Abstract

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 intra-molecular 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 intra-molecular interactions with each other. These findings may be extended to other MFS members to understand conserved and evolving mechanisms underlying transporter structure-function relationships.

Type: Article
Title: Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.260059
Publisher version: https://doi.org/10.1242/jcs.260059
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Arrestins, Cytosolic termini, Endocytosis, Major facilitator superfamily (MFS), Monocarboxylic acids, Transporters
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10147346
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