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.
Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity
The authors contributed equally to the work
- Award Group:
- Funder(s): Fundacao para a Cioncia e a Tecnologia (FCT) I.P.
- Award Id(s): UIDB/04050/2020
- Funder(s):
- Award Group:
- Funder(s): European Regional Development Fund
- Award Id(s): PTDC/BIA-MIC/5246/2020
- Funder(s):
- Award Group:
- Funder(s): Fondation Sant
- Award Id(s): KE17237
- Funder(s):
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Cláudia Barata-Antunes, Gabriel Talaia, George Broutzakis, David Ribas, Pieter De Beule, Margarida Casal, Christopher J. Stefan, George Diallinas, Sandra Paiva; Interactions of cytosolic tails in the Jen1 carboxylate transporter are critical for trafficking and transport activity. J Cell Sci 2022; jcs.260059. doi: https://doi.org/10.1242/jcs.260059
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