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.
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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-pp.ucl.ac.uk/id/eprint/10147346 |
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